Peptide Synthesis Methods Quiz

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Questions and Answers

What is the primary method used to synthesize tripeptides in the Mix and Split Method?

Sequential synthesis of individual amino acids.

Mixing and partitioning of amino acids. (correct)

Combination of pre-synthesized tripeptides.

Direct synthesis on solid supports.

How many total tripeptides can be synthesized using 3 different amino acids according to the Mix and Split Method?

54 tripeptides

9 tripeptides

27 tripeptides (correct)

81 tripeptides

What is one key characteristic of solution phase synthesis?

Molecules are synthesized primarily in liquid solution. (correct)

It only works with small peptides.

Molecules are always attached to a solid support.

Reactions occur exclusively in gaseous form.

What is the approximate number of hexapeptides that can be produced when using 20 different amino acids?

34 million hexapeptides total Signup and view all the answers

Which of the following statements is true regarding the testing of synthesized tripeptides?

All synthesized tripeptides are synthesized and tested for activity. Signup and view all the answers

What is the main purpose of using Merrifield resin in peptide synthesis?

To provide a solid support for peptide assembly Signup and view all the answers

What does the term 'Parallel Synthesis' refer to in the context of organic chemistry?

The synthesis of one compound in multiple vessels Signup and view all the answers

Which amino acid residue do all possible tripeptides in the active mixture end with?

Valine Signup and view all the answers

Which of the following compounds is an example of a t-butyl ester?

TertBu ester Signup and view all the answers

In peptide synthesis, what is typically the role of the deprotection step?

To remove protecting groups from amino acids Signup and view all the answers

What is the significance of adding valine to the retained dipeptide mixtures?

It identifies the specific active tripeptides. Signup and view all the answers

Why is it advantageous to know the identity of each structure in Parallel Synthesis?

It allows for the optimization of specific analogues for selected targets Signup and view all the answers

Which of the following statements is true regarding the mixtures presented?

The active component is narrowed down to one of three possible tripeptides. Signup and view all the answers

What is the function of the chloromethyl group in Merrifield resin?

To facilitate the binding of amino acids Signup and view all the answers

Which methodology is employed to analyze the structures formed during synthesis?

Recursive deconvolution Signup and view all the answers

What outcome is expected after synthesizing each of the identified tripeptides?

They will be tested for activity. Signup and view all the answers

What is typically released from the solid support at the end of peptide synthesis?

The synthesized peptide Signup and view all the answers

Which amino acid appears most frequently in the mixtures presented?

Glycine Signup and view all the answers

Which of the following esters includes a trimethylsilyl group?

Tmse ester Signup and view all the answers

Why are some mixtures labeled as inactive?

They do not produce desirable activity results. Signup and view all the answers

What is the primary purpose of performing a recursive deconvolution in this context?

To separate and identify active components. Signup and view all the answers

What is the primary objective of Combinatorial Chemistry?

To generate a large number of molecules quickly and cost-effectively. Signup and view all the answers

What advantage does Combinatorial Chemistry provide in drug discovery?

It increases the probability of finding novel compounds. Signup and view all the answers

Which method is NOT mentioned as a tool in Combinatorial Chemistry?

High Throughput Screening Signup and view all the answers

In what way does Combinatorial Chemistry speed up the drug synthesis process?

By enabling the synthesis of multiple compounds simultaneously. Signup and view all the answers

What is the role of solid phase techniques in Combinatorial Chemistry?

They allow reactants to be modified while still attached to a surface. Signup and view all the answers

How does Combinatorial Chemistry differ from traditional drug discovery methods?

It can produce millions of compounds in a fraction of the time. Signup and view all the answers

What does the term 'Parallel Synthesis' refer to in Combinatorial Chemistry?

Simultaneous creation of multiple compounds with similar structures. Signup and view all the answers

What is one of the key benefits of using a mixed combinatorial synthesis approach?

It saves effort by producing a diverse library at once. Signup and view all the answers

What does SCAL stand for in the context of tagging?

Safety CAtch Linker Signup and view all the answers

Which amino acid is indicated in the tagging example?

Tryptophan Signup and view all the answers

Which step involves the introduction of Tag 1 in the synthesis process?

Step 1 Signup and view all the answers

What is the chemical group that appears in the synthesized product during Step 3?

Chloro group Signup and view all the answers

Which amino acids are labeled as aa1 and aa2 in the tagging example?

Lysine and Tryptophan Signup and view all the answers

What is the role of a 'tag' in mixed combinatorial synthesis?

To modify the amino acid structure Signup and view all the answers

What is the purpose of the NH2 group in the provided tagging structure?

To function as an amine group Signup and view all the answers

In the tagging example, what is the function of Tag 2?

To initiate the reaction with aa2 Signup and view all the answers

What is the primary aim of planning a combinatorial synthesis?

To generate a diverse range of compounds Signup and view all the answers

Which of the following is NOT one of Lipinski’s 'Rule of Five' for oral activity?

A calculated log P value greater than +5 Signup and view all the answers

In combinatorial synthesis, what is the role of a molecular core or scaffold?

To provide a structural basis for functionality attachment Signup and view all the answers

What makes photolithography an example of combinatorial synthesis?

It can create a large number of different outputs from one structure Signup and view all the answers

What is contained within the structure represented by 'NHX' in the synthesis process?

An amino acid residue Signup and view all the answers

Why is increasing the chances of finding a lead compound important in combinatorial synthesis?

To enhance compound efficiency in binding sites Signup and view all the answers

Which of the following statements about deprotection in combinatorial synthesis is true?

It removes protective groups to create reactive sites Signup and view all the answers

What purpose do substituent 'arms' serve in a combinatorial synthesis framework?

To enhance target specificity for binding Signup and view all the answers

Signup and view all the answers

Study Notes

Combinatorial Chemistry Overview

Combinatorial chemistry is a method used to reduce drug discovery time and costs.
Scientists use it to create a large number of molecules that can be efficiently screened.
Applications span pharmaceutical, biotechnology, and agro chemistry.

Strategies for Combinatorial Chemistry

Conventional: One molecule at a time, making, testing purity of hundreds of molecules a month. Slow lead generation, high risk of failure.
Combinatorial: Many molecules at a time, making, testing purity of thousands of molecules a month. Faster lead generation, low risk of failure.
Synergy: Both conventional and combinatorial strategies combine for efficiency in lead identification.

Applications of Combinatorial Chemistry

Scientists use combinatorial chemistry to generate large populations of molecules for screening.
Larger and more diverse compound libraries improve the probability of finding novel compounds with significant therapeutic and commercial value.

Advantages of Combinatorial Chemistry

Fast: Creation of millions of compounds in the same time it takes to make one compound using traditional methods.
Economical: Negative results from mixtures save the effort of synthesizing, purifying, and identifying individual compounds.
Easy: Isolating, purifying, and identifying active molecules from combinatorial libraries is relatively straightforward.
Drug Discovery: Mixed combinatorial synthesis produces a chemical pool, with the probability of finding an active molecule being proportional to the number of molecules in the pool.
Drug Optimization: Parallel synthesis creates analogues with slight differences, speeding up the lead optimization process.

Combinatorial Chemistry within Drug Design

Starts with a therapeutic target.
Leads to discovery of a lead compound.
Refinements lead to lead optimization.
The final stage involves the development of a candidate drug.
The entire procedure can be significantly affected by combinatorial chemistry.

Impact of Combinatorial Chemistry at Lead Discovery Phase

Traditionally, lead drugs came from natural products, custom-made organic molecules, and analogues of known active compounds.
High throughput screening (HTS) needs a large number of compounds to be effective, which combinatorial chemistry provides.

Tools for Combinatorial Chemistry

Solid-Phase Techniques: Reactants bind to a polymeric surface for modification during synthesis. The final product is released afterward.
- Requirements include a resin bead or similar surface, a linker to attach the reactant, a way to cleave the product from linker after synthesis, and protecting groups for functional groups.
- Examples: Partially cross-linked polystyrene beads, Sheppard's polyamide resin, Tentagel resin, and functionalised glass surfaces.
Parallel Synthesis: Standard synthetic routes are used to create diverse analogues, and the identity of each structure is known.
Houghton's Tea Bag Procedure: A manual, yet potentially inexpensive method, for separate reactions on beads in teabags.
Automated Parallel Synthesis: Automated systems for large-scale parallel synthesis, using 42, 96, or 144 reaction vessels.
Mixed Combinatorial Synthesis: Standard synthetic routes are used to produce a variety of analogues, where mixtures of products are present in each vessel. The identities of individual molecules are frequently unknown. Uses the mix and split method.
The Mix and Split Method: A key strategy in mixed combinatorial synthesis, where the products from prior stages are combined and split into separate vessels for the next synthesis steps.

Synthesis Protecting Groups Application

Protecting groups are used to shield functional groups during synthesis.
Amines' protecting groups include Boc (t-butoxycarbonyl), Fmoc (9-fluorenylmethoxycarbonyl), and Tmsec (2 trimethylsilyl ethoxycarbonyl).
Carboxylic acids' protecting groups include tert-butyl esters (t-Bu) and Fm or Tmse esters.

Identification of Structures from Mixed Combinatorial Synthesis

Recursive Deconvolution: A method for identifying an active component in a mixture, enabling more efficient identification relative to synthesizing all possibilities from scratch.
Tagging: Modifying molecules with tags (like SCAL) for identification, allowing the tracking of the molecules throughout the synthesis.
Photolithography: Using light to selectively activate or deactivate certain regions of a surface, enabling precise control over the synthesis process.

Planning Combinatorial Chemistry Synthesis

Aims: To create a large collection of diverse compounds, increasing the chances of finding a lead compound that fits a binding site. Typically follows Lipinsky's rule of five to ensure the drug is orally active and has low molecular weight. Scaffolds are used to organize the synthesis around a core structure/molecular skeleton
Scaffolds: Using a core structure aids in optimization by applying similar function and shape to different molecules.
Tadpole versus Spider scaffolds: In tadpole scaffolds variation is limited to a specific region, while spider scaffolds allow better diversification.
Examples and Poor Examples: Certain types of scaffolds are preferred for their functionality and suitability, while others are not optimal for diverse molecule creation.

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Description

Test your knowledge on various peptide synthesis methods, specifically focusing on the Mix and Split Method and Parallel Synthesis. This quiz covers key characteristics, synthesis calculations, and the roles of different components in the process. Perfect for students of organic chemistry and biochemistry!