Ch. 3 Amino Acids and Polypeptides

most amino acids are ___ configuration

L

L-amino acid has its amino group (-NH₂) on the left side

common amino acid structure (@physiological pH)

amino acid functions as a zwitterion

R group categories

1. nonpolar

2. uncharged polar

3. charged polar

__ standard proteinogenic amino acids

20

9 essential amino acids

the 2 special proteinogenic amino acids

selenocysteine

pyrrolysine

what are proteinogenic a.a.?

amino acids that are added during the process of translation to build proteins

non-ribosomal peptides

a.a. utilizes and assembled by enzymes rather than ribosomes

post-translationally modified amino acids

a.a. that are altered or added chemically after the protein translation process is complete

amino acids with nonpolar side chains

1. Glycine

2. Alanine

3. Valine

4. Leucine

5. Isoleucine

6. Methionine

7. Phenylalanine

8. Tryptophan

9. Proline

Glycine

Gly

G

Alanine

Ala

A

Valine

Val

V

Leucine

Leu

L

Isoleucine

Ile

I

Methionine

Met

M

Proline

Pro

P

Phenylalanine

Phe

F

Tryptophan

Trp

W

Amino acids with uncharged polar side chains

can do H bonding

Serine

Threonine

Cysteine

Asparagine

Glutamine

Tyrosine

Serine

Ser

S

Threonine

Thr

T

asparagine

Asn

N

Glutamine

Gln

Q

Tyrosine

Tyr

Y

** can sometimes be partially ionized

Cysteine

Cys

C

**can sometimes be partially ionized

Amino acids with ionized polar side chains

Acidic amino acids (NEGATIVE) — anionic

• aspartic acid

• glutamic acid

Basic amino acids (POSITIVE) — cationic

• arginine

• lysine

• histidine

Glutamate (Glutamic acid)

Glu

E

Aspartate (Aspartic Acid)

Asp

D

Arginine

Arg

R

Histidine

His

H

Lysine

Lys

K

pKa of the amino group on a.a.

pKa = 9-10

if there is a negative charge nearby, the pKa increases

pKa of the carboxylate group on a.a.

pKa = 2-3

if positive charge nearby, pKa decreases

amphoteric

can act as both acid and base

Imidazole group of Histidine

• polar chains are partially ionized

• imidazole groups can potentially be amphoteric

cysteine can form…

disulfide bonds

a.a. nomenclature

Naming amino acids

1. start at the amino terminus (N-terminus)

2. for all by last a.a. change the suffix to -yl

3. end at the carboxyl terminus (C-terminus)

which standard amino acid is an exception to chirality

glycine

R-group has 2 H

What are the 3 methods or properties for classifying and describing a.a. stereochemistry?

optical activity (+ or -) rotation of plane-polarized light

D/L system (relative configuration)

R/S system

polarimeter

direction and angle of rotation can be measured using polarimeter

optically active substance in solution in the tube causes the plane of the polarized light to rotate

optical activity — only determined experimentally

• dextrorotary = (+)

• levorotary = (-)

enantiomers

molecules that are nonsuperimposable on each other

order of priority of some common functional groups:

1. SH

2. OH

3. NH2

4. COOH

5. CHO

6. CH2OH

7. C6H5

8. CH3

9. H

most a.a. are S enantiomers except

cysteins

drugs are typically synthesized as racemic mixtures…

• Ibuprofen: S-enantiomer is much more active that R

• Thalidomide: drug for bone marrow cancer/multiple myeloma, S-thalidomide is a teratogenic compound

phosphorylation of amino acids

carboxylation of a.a.

hydroxylation of a.a.

methylation of a.a.

acetylation of a.a.

green fluorescent protein

• can be expressed in living multicellular organisms (such as mice or fish), causing them to glow when exposed to ultraviolet light

• polypeptide of 238 a.a. residues

• light-emitting group (fluorophore) is formed by a specific sequence of Serine (Ser), Tyrosine (Tyr), and Glycine (Gly)

  • these residues undergo a cyclization to create a heterocycle, which forms the active fluorophore responsible for the green fluorescence

Biologically active amino acids can

• transport N (in form of amino groups)

• be oxidized as metabolic fuels to provide energy

• function as chemical messengers (a.a.-derived hormones)

Glutathionone

ripeptide composed of Glu - Cys - Gly

gamma-carboxylate of glutamate forms an isopeptide bond with the amino group of the cysteine residue

serves as an antioxidant — serves as a buffer that helps prevent oxidative damage to proteins by neutralizing reactive species

Dimerization of Glutathionone

• Oxidation to GSSG: Two molecules of reduced glutathione undergo oxidation, linking their thiol groups together to form a dimeric disulfide-linked molecule called glutathione disulfide

• Reduction: This reaction is fully reversible; GSSG can be reduced back into two molecules of GSH

dimer helps prevent damage to protein

For a protein of n residues, there are ___ possible sequences

20ⁿ possible sequences

primary protein structure

ordered amino acid sequence of its polypeptide chain

condensation of 2 amino acids

Disulfide Bonds in the Primary Structure of Bovine Insulin

shows us that the primary structure = linear a.a. sequence & contains all info needed for protein folding and where covalent cross-links (like disulfide bonds) form