Biochemistry Basics Quiz

Lecture Information

• Course: PHAR 7813 Principles of Drug Action I
• Lecture: 5
• Topic: Understanding Drugs on the Molecular Level: Stereochemistry and Molecular Introduction to Biomolecules
• Date: January 31st, 2023
• Instructor: Anthony W. G. Burgett, Ph.D.

Learning Objectives: Stereochemistry

• Define stereochemistry, isomer, conformational isomer, substituents, and stereoisomers.
• Describe conformational isomers and their limitations in drug molecules.
• Identify sp² hybridized functional groups that can have multiple stereoisomers based on substituents.
• Identify requirements for an sp³ tetrahedral carbon to be a stereocenter.
• Define chirality, asymmetry, stereochemical configuration, enantiomers, and diastereomers.
• Identify possible stereochemical configurations around an sp³ stereocenter and name them.
• Explain why enantiomers have identical physical properties but different drug properties.
• Understand how a molecule with two stereocenters has two sets of enantiomers that are diastereomers to each other.
• Define and recognize a racemic mixture and its existence in a molecule based on its structure.

Learning Objectives: Biomolecules

• List and identify the four major classes of biomolecules based on their structure.
• Define the lipid class of biomolecules.
• Describe how lipids organize into bilayers and identify lipid classes.
• Identify steroids, fatty acid lipids, triglycerides, and phospholipids based on their structures.
• Define and recognize amino acids, peptides, and proteins.
• Identify the four parts of an amino acid.
• Explain why proteins can be considered to have stereochemistry.
• Define and recognize carbohydrates in open form, closed forms, 3D drawings, and polymeric forms (e.g., glucose, ribose).
• Recognize monosaccharides, disaccharides, and polysaccharides and their stereoisomer forms.
• Identify the three components that make up nucleotides and how they polymerize into nucleic acids (DNA and RNA).
• Recognize that nucleotides have biological activities besides forming DNA/RNA.
• Identify ribose and deoxyribose in open and closed forms and the 5 nucleobases (e.g., adenine, cytosine, thymine, uracil, guanine) related to nucleotides.
• Explain the molecular structural differences between DNA and RNA.

Understanding Drugs on the Molecular Level

• Stereochemistry greatly influences drug molecule form and function (illustrated with naproxen).
• The precise arrangement of atoms (stereochemistry) is vital for a drug to bind to its target protein.
• Different stereochemical configurations of a compound can lead to drastically different interactions with proteins, influencing drug effectiveness.

Organic Chemistry Review of Stereochemistry

• Isomers are different compounds with the same molecular formula.
• Stereoisomers have the same connectivity but different 3D arrangements.
• Constitutional isomers have different bonding patterns.
• Configurational isomers cannot be converted by rotating around single bonds (e.g., sp² carbons, alkane groups).
• Conformational isomers can be converted by rotating around single bonds.
• Enantiomers are nonsuperimposable mirror images.
• Diastereomers are stereoisomers that are not mirror images.
• Geometric Isomers (sp²) have no stereocenters; Optical Isomers (sp³) have stereocenters.

Understanding sp³ Chiral Stereocenters

• A molecule with an sp³ hybridized carbon atom with four different substituents is chiral.
• The four different configurations create two non-superimposable mirror images called enantiomers (denoted as R or S).

Diastereomers

• Diastereomers differ in configuration at two or more stereocenters.
• They have different properties because they are not mirror images and therefore are not enantiomers.

Racemic Mixture

• A racemic mixture contains equal amounts of both enantiomers of a chiral compound.
• The mixture shows squiggly lines between the chiral center and its substituents.
• Historically, this meant drug manufacturing did not focus on separate pure enantiomers but now there is increased focus on single enantiomer preparation due to vastly different therapeutic effects.

Molecular Introduction to Biomolecules

• Major biological molecules include nucleic acids (DNA and RNA), proteins, carbohydrates, and lipids.
• Lipids are categorized by their features and poor aqueous solubility.
• Main types of molecules of Lipids are: triglycerides, fatty acids, phospholipids, and steroids.
• Nucleic acids consist of nucleotides.
• Proteins are polymers of amino acids.
• Carbohydrates can be monosaccharides, disaccharides, or polysaccharides.