Lecture 4: Amino acid and protein chemistry

protein functions

structural, signaling, catalysts, immunity, regulation, poisons, transport

protein

building blocks of life

Amino Acids

Building Blocks of Protein

proteins are made of

linear heteropolymers of α-amino acids

zwitterion (dipolar ion)

molecule that contains both positive and negative charges but can have an overall net charge of zero

Carboxyl group at Physiological pH

Loses H⁺ (deprotonates) → becomes –COO⁻, negatively charged

Amino group at Physiological pH

Accepts H⁺ (protonates) → becomes –NH₃⁺, positively charged

amino acid is zwitterion

bc its amino and carboxylate group equal to 0 net charge

isoelectric point (pI)

pH where the amino acid has an average net charge of zero, neutral zwitterion

isoelectric point (pI) of neutral aa (13)

average of pKa₁ and pKa₂

isoelectric point (pI) of acidic aa (4)

average of the two lowest pKa

isoelectric point (pI) of basic aa (3)

average of the two highest pKa

peptide bond

chemical bond formed between two AAs molecules
when the carboxyl group of one AA reacts with the amino group of the other, releasing a molecule of water

primary structure of a protein

order in which the individual AAs making up the protein are linked together through peptide bonds

Secondary Structure of Protein

three main secondary structures formed by hydrogen bonds: the α-helix, β-pleated sheet, and β-turn

α-helix

hydrogen bonding b/t peptide bonds

β-pleated sheet

antiparallel arrangement

β-turn

hydrogen bonding between the 1st and 3rd peptide bond

Tertiary Structure of Protein

crucial to their function and interaction with drugs

bonds and interactions b/t R-groups, or b/t R groups, and peptide bonded backbone

Quaternary Structure of Protein

involve interactions between the exterior surfaces of proteins and it is also possible for protein molecules
to interlock in a quaternary structure

bonds b/t R groups, and b/t peptide backbone of different polypeptide

hemoglobin

possesses quaternary structure as it is made up of
four protein molecules

2 identical alpha subunits and two identical beta subunits

proteins as drug targets:

receptors, enzymes, carrier proteins, structural proteins

protein therapeutics:

Group I:Protein therapeutics with enzymatic or regulatory activity

Group II: Protein therapeutics with special targeting activity

Group III: Protein vaccines

Group IV: Protein diagnostics

Group I:Protein therapeutics with enzymatic or regulatory activity

proteins that replace, enhance, or provide a biological function

Group I protein examples

Ia: Replacing a protein that is deficient or abnormal
Ib: Augmenting an existing pathway
Ic: Providing a novel function or activity

Group II: Protein therapeutics with special targeting activity

proteins that target specific molecules, cells, or organisms

Group II Protein examples

IIa: Interfering with a molecule or organism
IIb: Delivering other compounds or proteins

Group III: Protein Vaccines

proteins that stimulate or modify the immune system

Group III: Protein examples

IIIa: Protecting against a deleterious foreign agent
IIIb: Treating an autoimmune disease
IIIc: Treating cancer

insulin

Group Ia (protein replacement)

Monoclonal antibodies

Group IIb (Protein Therapeutics with Special Targeting Activity)

COVID 19 Spike Protein and Antibody/Vaccines

Group IIa = Target and block

Group IIIa = Vaccinate and protect