Medicinal Chemistry Quiz Overview
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Questions and Answers

What is the primary role of the course TA?

  • To assist students with course material and answer questions (correct)
  • To design and deliver lecture content
  • To grade quizzes and exams
  • To create the course syllabus and set grading policies

According to the syllabus, what aspect of the final exam is NOT cumulative?

  • The material covered in the midterm
  • The material covered in the lectures
  • The material covered in the discussions
  • The material covered in the quizzes (correct)

Which of the following is NOT a course objective stated in the provided content?

  • Differentiating between small and large molecule drugs
  • Comprehending major drug classifications
  • Understanding drug discovery and design
  • Analyzing the social impact of drug development (correct)

What is the purpose of the discussion groups?

<p>To facilitate student collaboration and problem-solving (A)</p> Signup and view all the answers

What is the weight of the quizzes in the overall course grade?

<p>20% (A)</p> Signup and view all the answers

If a student misses one quiz, what can they do to minimize the impact on their overall grade?

<p>Drop their lowest quiz score at the end of the quarter (C)</p> Signup and view all the answers

What are the two dates mentioned in the syllabus for in-person exams?

<p>February 6th and March 13th (B)</p> Signup and view all the answers

What is the primary focus of 'Medicinal Chemistry II—Blockbusters' course mentioned in the syllabus?

<p>Understanding the development and impact of blockbuster drugs (D)</p> Signup and view all the answers

What is a characteristic of covalent binding interactions?

<p>They are often non-reversible. (C)</p> Signup and view all the answers

Which type of bond is considered the strongest among intermolecular bonds?

<p>Ionic Bonds (C)</p> Signup and view all the answers

What is the main focus of pharmacodynamics?

<p>The interaction between a drug and its target to produce effects. (C)</p> Signup and view all the answers

Which statement is true about bioisosteres?

<p>They exhibit structural and functional similarities. (A)</p> Signup and view all the answers

What does a high therapeutic index indicate?

<p>A large safety margin between beneficial effects and harmful effects. (D)</p> Signup and view all the answers

What defines the principle of selective toxicity in drug design?

<p>Drugs that target foreign or abnormal cells while sparing healthy ones. (B)</p> Signup and view all the answers

What is the role of hydrogen bonds in binding interactions?

<p>Hydrogen bonds form between electron-rich and electron-deficient atoms. (C)</p> Signup and view all the answers

Which of the following interactions is not considered a type of non-covalent binding?

<p>Covalent Bonds (B)</p> Signup and view all the answers

Which of the following BEST describes the role of 'binding groups' in drug-target interactions?

<p>Binding groups are specific functional groups on the drug that recognize and interact with the target. (A)</p> Signup and view all the answers

What is the primary difference between 'enantiomers' and 'diastereoisomers' in terms of stereochemistry?

<p>Enantiomers have opposite configurations at all stereocenters, while diastereoisomers have opposite configurations at only some stereocenters. (D)</p> Signup and view all the answers

Which of the following is NOT a type of key reaction commonly encountered in organic chemistry, particularly in drug design?

<p>Hydrolysis (D)</p> Signup and view all the answers

Which of these molecules is categorized as an insecticide based on the provided information?

<p>N-methylnicotine (D)</p> Signup and view all the answers

What is the key structural difference between the structures of 'Nicotine' and 'N-methylnicotine'?

<p>Nicotine has a nitrogen attached to a hydrogen atom, while N-methylnicotine has a nitrogen attached to a methyl group. (C)</p> Signup and view all the answers

Which of the following actions would NOT be considered academic dishonesty in an online quiz setting?

<p>Using a calculator to perform calculations during a math-based online quiz. (D)</p> Signup and view all the answers

When is it permissible to sell or distribute course lecture notes or recordings?

<p>When the university has granted explicit permission in advance. (D)</p> Signup and view all the answers

Which of the following is NOT mentioned in the text as a form of academic dishonesty during an exam?

<p>Plagiarizing content from a textbook during an exam. (B)</p> Signup and view all the answers

What is the main purpose of the 'Course Materials' section of the text?

<p>To outline the consequences of academic dishonesty related to course materials. (A)</p> Signup and view all the answers

What is the most severe consequence of academic dishonesty?

<p>A failing grade in the course. (D)</p> Signup and view all the answers

Which of the following topics is NOT discussed in the second week of lectures?

<p>Drug Delivery and Formulation. (D)</p> Signup and view all the answers

What is the primary focus of the course, as indicated by the lecture titles?

<p>Pharmacology and Drug Development. (B)</p> Signup and view all the answers

Why does the pKa of the carboxylic acid group in an amino acid shift from 4.8 (typical acid) to 2.3?

<p>The charge-charge repulsion between the positively charged amine and the partially positive charge on the departing proton of the carboxylic acid group lowers the pKa. (C)</p> Signup and view all the answers

What is the primary reason for the pKa shift of the amine group in an amino acid, from 10.6 (typical amine) to 9.6?

<p>The proximity of the negatively charged carboxylic acid group pulls electrons away from the amine, making it easier to remove a proton. (C)</p> Signup and view all the answers

What is the main factor contributing to the uniqueness of each amino acid?

<p>The unique functional group present in the side chain. (C)</p> Signup and view all the answers

Which statement BEST describes the reason why pKa values of amino and carboxyl groups in amino acids are different from those observed in simple molecules?

<p>The interactions between the amino and carboxyl groups within the amino acid molecule affect their pKa values. (C)</p> Signup and view all the answers

Which of the following factors would LEAST likely influence the pKa of a side chain in an amino acid?

<p>The specific sequence of amino acids in the protein. (B)</p> Signup and view all the answers

What is the significance of knowing the pKa values of amino acid side chains?

<p>It helps understand the charge state of a protein at a particular pH. (B)</p> Signup and view all the answers

Which of the following statements accurately describes the relationship between pKa and side chain functional groups?

<p>The pKa value of a side chain depends on its functional group, influencing its charge state at a particular pH. (A)</p> Signup and view all the answers

How does the understanding of pKa values contribute to the development of drugs that interact with proteins?

<p>All of the above are correct. (D)</p> Signup and view all the answers

Which of the following statements BEST describes the concept of 'induced fit' in enzyme catalysis?

<p>The active site of an enzyme undergoes a conformational change to accommodate the substrate, forming a more specific and stable interaction. (C)</p> Signup and view all the answers

What is the primary role of the catalytic triad in chymotrypsin?

<p>To provide a proton donor and acceptor to facilitate the hydrolysis of the peptide bond. (A)</p> Signup and view all the answers

Which of the following is a key difference between ATP-competitive and non-ATP competitive inhibitors?

<p>ATP-competitive inhibitors bind to the same site as ATP, while non-ATP competitive inhibitors bind to a different site. (C)</p> Signup and view all the answers

Which of the following BEST describes the purpose of an alanine scan in drug development?

<p>To identify the amino acid residues that are essential for binding to the target protein. (A)</p> Signup and view all the answers

What is the primary difference between 'allosteric regulation' and 'competitive inhibition' of enzymatic activity?

<p>Allosteric regulation involves binding to a site distinct from the active site, while competitive inhibition occurs at the active site. (C)</p> Signup and view all the answers

Which of the following statements BEST describes the mechanism of action of TPCK as an inhibitor of chymotrypsin?

<p>{ &quot;A&quot;: &quot;TPCK forms a covalent bond with the active site serine, irreversibly inactivating the enzyme&quot;, &quot;B&quot;: &quot;TPCK binds to the active site histidine, preventing the formation of the catalytic triad&quot;, &quot;C&quot;: &quot;TPCK acts as a substrate analog, competing with the natural substrate for binding to the active site&quot;, &quot;D&quot;: &quot;TPCK stabilizes the transition state, preventing the hydrolysis of the peptide bond&quot; } (A)</p> Signup and view all the answers

What is the significance of targeting kinases as drug targets?

<p>Kinases play a crucial role in regulating cell signaling pathways, making them viable targets for treating various diseases. (D)</p> Signup and view all the answers

How do non-ATP competitive inhibitors of MEK1 potentially achieve selectivity over other kinases?

<p>They target a specific allosteric pocket that is unique to MEK1, minimizing off-target effects. (D)</p> Signup and view all the answers

Based on the provided information, what is the primary reason why Mycobacterium tuberculosis and certain yeasts rely heavily on endogenous riboflavin production for survival?

<p>These organisms exhibit a compromised riboflavin uptake system, making them dependent on internal production. (D)</p> Signup and view all the answers

Which of the following most accurately describes the significance of the Tanimoto Index in the context of the provided information?

<p>The Tanimoto Index quantifies similarity between molecular structures, aiding in identifying potential drug candidates based on structural mimicry of known active compounds. (C)</p> Signup and view all the answers

Given the information about Hunanamycin A's discovery and its potential as an antibiotic, which of the following is the most likely strategy for developing new, structurally-related antibiotics based on this molecule?

<p>Synthesizing a variety of structurally different derivatives and screening them for antibiotic activity, focusing on modifying the core structure of Hunanamycin A. (C)</p> Signup and view all the answers

Based on the given information, what is a key characteristic of the marine bacterium SNA-048 that makes it a promising source for discovering new antibiotic compounds?

<p>The bacterium's unique natural habitat, a mangrove swamp, suggests it may produce novel compounds with diverse biological activities, including antibiotic potential. (A)</p> Signup and view all the answers

Based on the provided context, what can be inferred about the potential challenges associated with utilizing Hunanamycin A as a therapeutic drug?

<p>Hunanamycin A could exhibit low bioavailability due to its complex structure, requiring specialized delivery strategies to reach its target site. (A), The potential for developing resistance to Hunanamycin A may be significant, requiring ongoing research to develop new, related antibiotics that circumvent resistance. (C), The synthesis of Hunanamycin A is extremely complex and expensive, presenting a challenge to its large-scale production and affordability as a drug. (D)</p> Signup and view all the answers

What characteristic makes natural products particularly unique in drug development?

<p>They can have wild ring structures and multiple stereocenters. (A)</p> Signup and view all the answers

Which process is essential for isolating active compounds from natural products?

<p>Bioactivity-guided isolation. (B)</p> Signup and view all the answers

What is the primary function of HPLC in the context of natural product drug discovery?

<p>To separate and purify compounds based on their hydrophobicity. (D)</p> Signup and view all the answers

Why are natural products considered a significant source of new chemical entities (NCEs) in drug development?

<p>Their diversity and complexity often lead to novel pharmacophores. (A)</p> Signup and view all the answers

What is a challenging step in the use of natural products for drug screening?

<p>Harvesting a sufficient quantity of the biological source. (A)</p> Signup and view all the answers

Why might MG132 be a poor choice as a therapeutic drug?

<p>MG132 is a potent inhibitor of the proteasome, leading to the build-up of misfolded proteins in the cell. (A), MG132 is a non-specific proteasome inhibitor, potentially leading to off-target effects. (C), MG132 is a potent inhibitor of the proteasome, causing cellular stress when administered. (D)</p> Signup and view all the answers

What is the primary role of ubiquitin in the proteasome degradation pathway?

<p>Ubiquitin functions as a recognition tag, marking proteins for degradation by the proteasome. (A)</p> Signup and view all the answers

Which statement BEST describes the role of PROTACs in targeted protein degradation?

<p>PROTACs are bifunctional molecules that bridge a target protein with an E3 ligase, leading to its ubiquitination and proteasomal degradation. (A)</p> Signup and view all the answers

What is a key advantage of using antibody PROTACs compared to traditional PROTACs?

<p>Antibody PROTACs can be used to target proteins that are not accessible to traditional PROTACs. (B)</p> Signup and view all the answers

Based on the provided information, what is a potential limitation of light-activated PROTACs?

<p>They might not be suitable for targeting proteins located deep within cells. (C)</p> Signup and view all the answers

Why is the development of covalent PROTACs a significant advancement in this field?

<p>Covalent PROTACs can achieve higher target affinity, enhancing protein degradation efficiency. (B), Covalent PROTACs can overcome challenges associated with drug resistance by irreversibly interacting with the target protein. (C)</p> Signup and view all the answers

What is the primary significance of the Western blot assay in the context of PROTAC development?

<p>Western blot facilitates the quantification of the target protein degradation induced by PROTACs. (A)</p> Signup and view all the answers

What is the main rationale for targeting BRD4 as a therapeutic target in cancer development?

<p>BRD4 plays a key role in regulating gene expression related to cell proliferation and tumor growth. (C)</p> Signup and view all the answers

What is the key role of pKa values in understanding the behavior of amino acids within a cellular environment?

<p>pKa values indicate the pH at which an amino acid side chain is 50% protonated and 50% unprotonated, influencing its charge and interactions. (D)</p> Signup and view all the answers

What is the significance of the number of transitions observed during the titration of histidine?

<p>It reflects the number of ionizable groups present in the histidine molecule. (D)</p> Signup and view all the answers

Why are polar residues typically found on the outer surface of proteins?

<p>Polar residues create stronger interactions with water molecules, facilitating protein solubility and interaction with the aqueous environment. (D)</p> Signup and view all the answers

Which of the following statements accurately describes the role of disulfide links in protein tertiary structure?

<p>They act as covalent bonds between cysteine residues, contributing to the structural stability of proteins by forming cross-links. (A)</p> Signup and view all the answers

What is the primary function of post-translational modifications (PTMs) in protein biology?

<p>They add or remove chemical groups to proteins, altering their properties and influencing their function, localization, and interactions. (B)</p> Signup and view all the answers

Which of the following interactions is NOT a type of non-covalent interaction involved in tertiary structure?

<p>Disulfide bonds (A)</p> Signup and view all the answers

Which of the following statements best defines the concept of 'hydrophobic interactions' in protein folding?

<p>Hydrophobic interactions are based on the tendency of nonpolar amino acid side chains to associate with each other, minimizing contact with water molecules. (D)</p> Signup and view all the answers

What is the key role of tertiary structure in determining protein function?

<p>It defines the overall shape and three-dimensional arrangement of a protein, which influences its binding sites, catalytic activity, and interactions with other molecules. (D)</p> Signup and view all the answers

What is the purpose of the diazirine and benzophenone photoaffinity probes in the context of drug discovery?

<p>To selectively target and label specific proteins or enzymes for further analysis. (C)</p> Signup and view all the answers

What is the main purpose of the 'click chemistry' reaction using an azide or tetrazine in the context of drug discovery?

<p>To covalently link the drug molecule to a specific target protein, enabling its identification and characterization. (B)</p> Signup and view all the answers

What is the role of streptavidin in the context of drug discovery?

<p>To bind to biotin-labeled drug molecules, facilitating their purification and isolation. (D)</p> Signup and view all the answers

What is the most likely reason why the addition of an enrichment tag is crucial in the drug discovery process?

<p>To facilitate the identification and isolation of the target protein that interacts with the drug. (D)</p> Signup and view all the answers

What is the primary purpose of the 'Fluorescence Gel Imaging' technique in drug discovery?

<p>To visualize the target protein that binds to the drug under UV light. (D)</p> Signup and view all the answers

How does the covalent modification of a drug molecule with an alkyne, diazirine, or benzophenone moiety affect the drug's interaction with its target protein?

<p>It allows for the drug to be selectively targeted to and covalently linked to the target protein. (D)</p> Signup and view all the answers

What is the primary advantage of using a 'click chemistry' reaction using Tetrazine and a Trans-cyclooctene for covalent drug modification?

<p>It avoids the need for metal catalysts, like copper, which can be toxic to cells. (C)</p> Signup and view all the answers

What is the main purpose of utilizing common fluorophores like BODIPY, TAMRA, and AMC in drug discovery?

<p>To visualize and analyze the drug's interactions with its target protein at the molecular level. (A)</p> Signup and view all the answers

What is the primary reason why degrading a protein via the lysosome is a less desirable target for drug discovery than degrading a protein via the proteasome?

<p>Inhibiting lysosomal degradation is less likely to be effective in treating diseases. (A), The proteasome is a faster and more efficient protein degradation pathway. (B)</p> Signup and view all the answers

Based on the provided information, which of the following would NOT be considered a 'target engagement' strategy?

<p>Monitoring the concentration of a ligand or inhibitor in the cell. (A)</p> Signup and view all the answers

In the context of 'AUTAC', the 'C' stands for 'Characterization'. What does the 'A' stand for, given the overall theme of the provided content?

<p>Activity (C)</p> Signup and view all the answers

Considering the text's mention of 'TPD' and 'Degradation Quantitation', what conclusion can be drawn about the relationship between these concepts?

<p>TPD is a tool used to quantify the degradation of proteins. (B)</p> Signup and view all the answers

What is the primary challenge addressed by the Activity-Based Protein Profiling (ABPP) technique, as described in the content?

<p>Overcoming the limitations of using purified proteins in thermal shift assays for drug target engagement studies. (D)</p> Signup and view all the answers

Based on the provided information, what is the main reason why the FDA requires a well-documented mechanism of action (MOA) for drug approval?

<p>To minimize potential off-target effects and side effects. (D)</p> Signup and view all the answers

Why is the understanding of pKa values important in drug development, specifically in relation to amino acid side chains?

<p>Identifying potential binding sites for drugs on a protein target based on the pKa of specific amino acids. (A)</p> Signup and view all the answers

Considering the provided information about drug development and the importance of identifying drug-target interactions, which of the following statements BEST describes the role of 'binding groups' in drug-target interactions?

<p>Binding groups specifically interact with the target molecule's active site, contributing to the drug's selective binding and efficacy. (C)</p> Signup and view all the answers

What is the significance of targeting kinases as drug targets in the context of drug development, as highlighted in the provided text?

<p>Kinases are involved in a wide range of cellular processes, making them potentially druggable targets for diverse diseases. (D)</p> Signup and view all the answers

Flashcards

Small vs. Large Molecule Drugs

Understanding the fundamental differences in size, structure, and function between small and large molecule drugs.

Drug-Target Binding

The interactions that occur when a drug binds to its target, crucial for drug efficacy.

Pharmacokinetics

The study of how the body affects a drug, including absorption, distribution, metabolism, and excretion.

Pharmacodynamics

How a drug affects the body, including its biochemical and physiological effects.

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Drug Classifications

Major categories of drugs based on their chemical structure, therapeutic use, or mechanism of action.

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Drug Discovery

The process of identifying new candidate medications, including research and development strategies.

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Problem-Solving in Medicinal Chemistry

The application of analytical skills to solve problems related to drug design and action.

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Academic Honesty

The commitment to integrity in coursework, requiring that all submissions be the student’s own work.

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Academic Dishonesty

Any act of cheating, copying, or misconduct during academic evaluations.

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UCI Policies on Academic Honesty

Regulations outlining acceptable behavior and consequences for academic integrity violations.

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Drug Targets

Large molecules called macromolecules that drugs bind to.

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Consequences of Cheating

Cheating can lead to failing grades and disciplinary actions.

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Binding Sites

Hydrophobic clefts on macromolecules where drugs attach.

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Binding Groups

Functional groups on a drug that recognize the target.

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Online Exam Integrity

Expectations of honesty during online quizzes and exams.

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Course Materials Ownership

Course materials are the intellectual property of the university.

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Electrophile

An atom or molecule that accepts electrons.

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Enantiomers

Molecules that are mirror images of each other.

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Disciplinary Action

Formal consequences for violations of academic policies.

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Prof. Trader Lectures Overview

Lectures cover topics like drug targets and protein functions.

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Natural Products as Drugs

Study of how substances from nature are used in pharmaceuticals.

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Covalent Binding

A strong chemical bond formed by the sharing of electron pairs between atoms.

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Penicillin

An antibiotic that binds covalently and is non-reversible, targeting bacteria.

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Hydrogen Bonds

Attractive interactions between an electron-deficient hydrogen and an electron-rich atom (N or O).

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Ionic Bonds

Strong intermolecular bonds (20-40 kJ mol-1), also known as salt bridges in proteins.

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Selective Toxicity

The principle that useful drugs show harmful effects only on foreign or abnormal cells, not on healthy ones.

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Therapeutic Index

A measure comparing a drug's effective dose to its toxic dose; indicates safety margin.

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Amino Acids

Building blocks of proteins, there are 20 common types.

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1 and 3 Letter Codes

Each amino acid has a unique 1-letter and 3-letter abbreviation.

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pKa Value

The pH at which a functional group is 50% dissociated.

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Side Chain Functional Groups

Unique parts of amino acids that determine their properties.

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Electron Pulling Effect

Negatively charged carboxylic acid can lower pKa of nearby amines.

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Charge-Charge Repulsion

Positive charges between amine and carboxylic acid can affect pKa.

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Shifting pKa for Amino Acid

Amino group pKa shifts from 10.6 to 9.6 in amino acids.

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Shifting pKa for Carboxylic Acid

Carboxylic acid pKa shifts from 4.8 to 2.3 in amino acids.

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pKa values of amino acids

pKa values indicate whether amino acids are protonated (charged) or unprotonated (neutral) in biological systems.

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Histidine titration

Histidine has specific pKa values that affect its ionization and role in protein function during titration.

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Primary protein structure

The order of amino acids in a protein, written from N-terminal to C-terminal.

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Secondary protein structure

The folding of the polypeptide chain into structures like alpha-helices and beta-sheets due to hydrogen bonding.

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Tertiary protein structure

The overall 3D shape of a protein formed by interactions between side chains, including hydrophobic interactions, hydrogen bonds, and salt bridges.

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Quaternary protein structure

The assembly of multiple polypeptide chains into a single functional protein complex.

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Post-translational modifications (PTMs)

Covalent alterations to proteins after translation that can affect their function and activity.

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Disulfide links

Covalent bonds formed between cysteine residues that help stabilize the tertiary structure of proteins.

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Active Site

The part of an enzyme where substrate molecules bind and undergo a chemical reaction.

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Induced Fit Model

The concept that the active site of an enzyme changes shape to fit the substrate better upon binding.

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Acid/Base Catalysis

A catalytic mechanism where proton transfer occurs to enhance reaction rates.

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Nucleophilic Mechanism

A chemical mechanism where a nucleophile attacks an electrophile to form a bond.

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Chymotrypsin

An enzyme that cleaves peptide bonds preferentially next to aromatic amino acids.

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Allosteric Regulation

Regulation of an enzyme's activity through binding at a site other than the active site.

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Kinase

An enzyme that transfers a phosphate group from ATP to a substrate, often regulating activity.

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Alanine Scan

A technique used to identify important amino acids in the binding site of a protein by substituting them with alanine.

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Natural Products (NP)

Substances derived from living organisms used in drug development.

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Steps for Drug Development

Process includes sourcing, evaluating activity, and optimizing natural products.

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Bioactivity-Guided Isolation

A method using biological activity to isolate effective molecules from mixtures.

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Chromatography

Technique to separate components in a mixture based on their properties.

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High Performance Liquid Chromatography (HPLC)

An advanced form of chromatography for separating hydrophobic molecules.

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Riboflavin Synthase Inhibitor

A compound that inhibits the enzyme riboflavin synthase, disrupting riboflavin production.

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Hunanamycin A

A natural product screened for antibiotic properties from a marine bacterium.

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Marine Bacterium SNA-048

A bacterium isolated for its potential antibiotic properties, closely related to Bacillus hunanensis.

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Antibiotic SAR

Structure-Activity Relationship in antibiotics, analyzing how structural changes affect activity.

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16S rRNA Analysis

A method for identifying bacterial species based on ribosomal RNA sequences.

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Central Dogma

The framework explaining how genetic information flows from DNA to RNA to proteins.

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Proteasome

A cellular structure responsible for degrading unneeded or damaged proteins.

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Ubiquitin

A small protein that tags other proteins for degradation by the proteasome.

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E3 Ligase

An enzyme that mediates the attachment of ubiquitin to target proteins for degradation.

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Western Blot

A laboratory method used to detect specific proteins in a sample.

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BRD4

A protein that regulates transcription and is involved in cancer development.

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PROTACs

Chemical compounds that induce targeted protein degradation via E3 ligase.

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Covalent PROTACs

A type of PROTAC that forms a covalent bond with its target protein for degradation.

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Targeting to Lysosome

The process of directing proteins to the lysosome for degradation.

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Diazirine

A small molecule used for photo-crosslinking in drug discovery.

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Benzophenone

A compound that can absorb UV light and be used in various applications, including photochemistry.

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Click Chemistry

A modular reaction used to link compounds efficiently, often involving azides and alkynes.

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Fluorescence Gel Imaging

A technique to visualize proteins using fluorescent dyes; essential for analyzing protein interactions.

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Common Fluorophores

Fluorescent molecules like BODIPY and TAMRA used for imaging and tagging in biological studies.

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Biotin-Streptavidin Interaction

A strong binding interaction used for tagging and isolating proteins; high affinity (Kd ~10^-14 M).

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Cross-Linking

A method to create covalent bonds between proteins or molecular structures to study interactions and functions.

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Pharmacophore

The part of a molecule responsible for its biological activity; defines how a drug interacts with its target.

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CETSA

Cellular Thermal Shift Assay used for detecting target engagement of compounds on proteins.

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ABPP

Activity-Based Protein Profiling to identify covalent inhibitors of enzymes.

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Innate Immune System

The immune system's rapid, non-specific response to foreign bodies.

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Adaptive Immune System

Responsible for antigen-specific responses and memory against specific pathogens.

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Immunosuppression

A condition resulting in a weakened immune response, increasing disease susceptibility.

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Study Notes

Course Information

  • Course name: Medicinal Chemistry
  • Course numbers: PhrmSci 177, Chem 177, PharmSci 277
  • Instructor 1: Darci Trader ([email protected])
  • Instructor 2: Brian Paegel ([email protected])

Teaching Assistants (TAs)

  • Mohammad Hajjar ([email protected])
  • Dana Shevachman ([email protected])
  • TAs attend lectures and notify instructors of student questions
  • TAs hold office hours to clarify lecture and reading concepts
  • TAs lead discussion groups to clarify lecture material and solution problems

Course Syllabus

  • Grading: Midterm (40%), Final (40%), Quizzes (20%)
  • Exams: In-person during lecture periods; Feb 6th and Mar 13th. Bring a computer or device
  • Quizzes: Online, 10 multiple choice questions per quiz, 24-hour availability starting at 1 pm PST, lowest quiz score can be dropped.
  • DSC Students: 1.5x time on quizzes and exams. Send documentation to Prof. Trader ASAP

Course Objectives

  • Understand differences between small and large molecule drugs
  • Identify and predict interactions in drug-target binding
  • Understand pharmacokinetics (how the body affects the drug)
  • Understand pharmacodynamics (how the drug affects the body)
  • Understand major drug classifications
  • Understand drug discovery and design strategies and application using problem-solving skills
  • Prepare students for Medicinal Chemistry II

Academic Honesty

  • Academic dishonesty will result in a failing grade.
  • This includes copying from others, letting others copy, communicating answers during exams, using unauthorized notes or aids during exams, tampering with exams.
  • Refer to UCI policies on academic honesty (see aisc.uci.edu)

Online Quizzes/Exams

  • Academic honesty expected for all online assignments.
  • Leaving and reentering Canvas during online quizzes/exams is considered a violation of academic honesty and will result in a 0 score for that assignment.
  • Quizzes only have 10 minutes to complete so do not start until ready

Course Materials

  • Course materials are the intellectual property of the University of California
  • Selling, distributing, or preparing course materials without authorization is prohibited
  • Violations of policy can result in grievance charges

Professor Trader's Lectures

  • Week 1: Course Introduction & Overview of Drugs and Drug Targets, Protein Structure and Function
  • Week 2: Enzymes as Drug Targets, Natural Product as Drugs
  • Week 3: Targeted Protein Degradation (including continued material)
  • Week 4: Target Engagement Techniques, Immune System Modulators
  • Week 1, natural products: Natural products are a good source of new drugs. Examples and their effects were demonstrated.
  • Week 2, enzymes: Enzymes lower the activation energy of a reaction without changing free energy. Enzymes provide reaction surface, suitable environment, bring reactants together, weaken bonds & provide catalytic functions. Enzymes can be classified using EC numbers. Shape complementarity is key for substrate binding and enzyme activity. Binding alters enzyme shape (induced fit) to coordinate intermolecular forces and to strain substrate bonds. Key enzyme classifications (by EC numbers) are noted, including examples like oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.
  • Week 3, targeted protein degradation: Natural Products are a source of new drugs. A list of examples and their effects were shown. Key concepts involving protein degradation through proteasome and autophagy pathways were included; specific technologies like PROTACs are part of the lecture.
  • Week 4, Target Engagement Techniques: New techniques that involve protein binding or non-covalent/covalent binding were explored, including covalent irreversible inhibitors like penicillin and reversible covalent inhibitors.
  • Week 4, Non-covalent interactions: Four types of non-covalent bonds were discussed, including Hydrogen bonds, Ionic interactions, Hydrophobic interactions, and Van der Waals interactions. The use of bioisosteres to modify ADMET properties is explored. Bioisosteres are functional groups or molecules with chemical and physical similarities, which produce broadly similar biological properties. Specific examples (5-fluorouracil vs. uracil) illustrate this concept.
  • Further details on common bioisosteres (monovalent, divalent, tetravalent, rings) and their role in modifying ADMET properties are included; specific examples illustrating this concept, like 5-fluorouracil and uracil, are noted.
  • Specific examples of simple drugs (like Nicotine, Muscle Relaxant, Ciprofloxacin, and Anileridine) and their chemical structures are presented within the lecture notes and for practice problems.
  • Enzyme classifications (by EC numbers) are noted, including examples like oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.
  • The mechanism of action for enzymes are detailed, including LDH and its related inhibitors (e.g., TPCK). Chymotrypsin's catalytic mechanism and its detailed mechanism, involving the catalytic triad, are covered, including examples like nucleophilic mechanism and steps such as attacking amide bonds, proton transfers, and ester hydrolysis.

Review Topics

  • Overview of Key Topics and Chapter 1
  • Organic Functional Groups
  • Structures and three-letter codes for all 20 amino acids
  • Electrophile vs. Nucleophile
  • Practice naming functional groups and electrophilic/nucleophilic moieties
  • Practice finding and naming functional groups (examples included)
  • Resonance structures
  • Amide bond resonance
  • Examples for simple drugs: Nicotine (insecticide), Muscle Relaxant, Ciprofloxacin, and Anileridine
  • Enzyme classifications including oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases (classification by EC numbers)
  • Allostery
  • Mechanism of action for enzymes, such as LDH and its related inhibitors (e.g., TPCK); the catalytic mechanism and detailed steps for chymotrypsin are covered, including the catalytic triad.
  • Case study on BRD4 degradation and its role in embryogenesis and cancer development, highlighting how E3 ubiquitin ligases are hijacked to target BRD4 for degradation.
  • Chemical structures, concentration-dependent and time-dependent degradation analysis, controls, and strategies for targeting diseased cells in the case study.
  • Light-activated PROTACs; mechanisms underlying covalent PROTACs, chemical structures of several PROTACs (e.g., dBET6, MZ1, SNIPER), and their role in influencing ADMET properties are covered.
  • Antibody PROTACs as an example, are integrated, including their mechanism of action within a cell's environment to reach target molecules.
  • Covalent PROTACs and their limitations which are detailed.
  • Future directions and approaches in PROTAC design; specific examples of in silico approaches for PROTAC design (structures like PROTAC-1, SMARCA2, VHL) are noted.
  • Analysis of how to determine protein degradation using techniques like Western Blotting, along with an example using BRD4 degradation within a biological or cellular context.
  • The use of alanine scanning and other methods to analyze amino acid functional groups in binding sites, as observed in the case study, is included.
  • Topics on allostery and inhibition of allosteric enzymes, such as kinases are noted. Key concepts for inhibitors targeting kinases are included alongside descriptions of their mechanism of action, such as how they bind to achieve the desired inhibitor effects when targeting kinases, alongside protein kinase classifications (Serine/Threonine Protein Kinases (STPKS), Tyrosine Kinases (TKS), Dual Specificity Protein Kinases (DSPKs))
  • The design of MEK1 inhibitors is noted.

Stereochemistry

  • Enantiomers: One stereocenter
  • Diastereomers: Two or more stereocenters

Key Reactions

  • Substitution: Summary: Bond formation and breakage at same carbon atom in a nucleophilic substitution reaction. A Lewis base (nucleophile) forms a new bond to carbon and a bond breaks between carbon and a leaving group
  • Addition
  • Elimination
  • Rearrangement

Drugs and Drug Targets - Chapter 1 Discussion

  • How do drugs work? Binding to a target.
  • What is a target? Large molecules called macromolecules with special binding sites.
  • What does binding mean? Functional groups interact with specific sites on the target.
  • Binding sites are on the surface of macromolecules or the active site of an enzyme.

Types of Binding - Covalent

  • Non-reversible: Penicillin
  • Reversible

Non-Covalent Binding Interactions

  • 4 types: Hydrogen bonds, Ionic interactions, Hydrophobic interactions, Van der Waals interactions

Hydrogen Bonds

  • Between electron-deficient hydrogen and electron-rich heteroatom (N or O)
  • Electron-rich heteroatom is hydrogen bond acceptor (HBA)
  • Electron-deficient hydrogen is a hydrogen bond donor (HBD)
  • Optimal orientation: 180° (linear)

Ionic Bonds

  • Strongest intermolecular bonds (20-40 kJ/mol)
  • Also called 'salt bridges' in protein structures
  • Important initial interactions for drug-target binding

ADMET and Binding

  • Functional groups affect absorption, distribution, metabolism, excretion, and toxicity (ADME)
  • More details on ADMET later

Modifying ADMET Properties

  • Medicinal chemists use bioisosteres to modify chemical structures and maintain similar biological properties.
  • General trends, not strict rules.
  • Examples of bioisosteres are shown with 5-fluorouracil compared to uracil.

Other Common Bioisosteres

  • Monovalent, Divalent, Tetravalent, Rings

Medicinal Chemistry and Pharmacology

  • Pharmacodynamics: How a drug binds to a target for an effect (What the drug does to the body)
  • Pharmacokinetics: How a drug is absorbed, distributed, metabolized, and excreted (ADME) (What the body does to the drug).

Things to Keep in Mind

  • No drug is completely safe; all have side effects.
  • Therapeutic index: Measures beneficial effect at low doses vs harmful effects at high doses. High index means large safety margin.
  • Selective toxicity: Drugs target abnormal cells, not healthy host cells (principle of 'smart drugs')

Studying That Suits You

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Related Documents

Lecture 3: Drugs And Enzymes PDF
Lecture 4: Natural Products, Prof. Trader, Winter 2025 PDF
Trader Lecture 2 - Protein Structure and Function PDF
Degrading Proteins for a Therapeutic Response Lecture Notes PDF
Lecture 6 (Winter 2025)
Final Lecture For Exam 1 PDF

Description

This quiz is designed for students enrolled in Medicinal Chemistry (PhrmSci 177, Chem 177, PharmSci 277). It includes multiple choice questions to assess understanding of key concepts covered in lectures and readings. Quizzes are available online with a 24-hour completion window and contribute to the course grading.

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