AMINO ACID DERIVATIVES

Proteins are linear polymers whose monomeric building blocks are amino acids:

Key structural features:

Central carbon (known as the "alpha carbon") is tetrahedral and chiral (i.e. each of the
four functional groups are different)

The "R" functional group is known as the amino acid "side chain". There are 20 common
different amino acid side chains. This is what distinguishes one amino acid from
another.Amino acids are also known as "residues".

There is an amino group and carboxylic acid group. At pH 7.0 these are both (oppositely)
charged. Amino acids are therefore also zwitterions

Amino acid monomers are chemically linked to form linear polymers known as proteins:

Note: this is drawn "flat" for clarity, but the Ca are still tetrahedral (the H atom on the Ca is
also not shown in this diagram)
Key structural features:

A "peptide bond" is formed by a condensation reaction between the carboxylic acid of

one amino acid with the amino group of the next amino acid

The amino acid R1, at the "amino terminus" of the polymer is the "first" amino acid. The
residue (R3 in the above diagram) at the carboxyl terminal is known as the "last" amino
acid. These termini define the directionality of the protein.

Common amino acids

There are 20 common amino acids. They are composed of C, H, O, N and S atoms. They are
structurally and chemically different, and also differ in size and volume. Some are branched
structures, some are linear, some have ring structures. One of the 20 common amino acids is
actually an imino acid. A typical grouping of their chemical nature is as follows:

Nonpolar (hydrocarbons and one sulfur-containing amino acid). Dispersion forces and
hydrophobic effects predominate in their interactions. They cannot H-bond with water
and these side chains have a characteristic hydrophobic effect in water.

Polar uncharged. Contain functional groups that can H-bond with water and other
amino acids. Include C, H, O, N and S atoms.

Acidic. Contain a carboxylic acid functional group with a negative charge at neutral
pH. Can H-bond with water, can form ionic interactions, and can also serve as
nucleophiles or participate in acid-base chemistry.

Basic. Nitrogen containing bases (e.g. guanidino, imidazole or amino groups) with a
net positive charge at neutral pH. Can serve as proton donors in chemical reactions,
and form ionic interactions.

The amino acids have a name, as well as a three letter or single letter mnemonic code:

Type

Name

Leucine
Nonpolar
Leu, L

Isoleucine
Ile, I

Valine
Val, V

Alanine
Ala, A

R-group Structure

Methionine
Met, M

Phenylalanine
Phe, F

Tryptophan
Trp, W

Proline
Pro, P

Glycine
Gly, G
(note: sometimes
included in polar
group)

Polar,
uncharged

Serine
Ser, S

Asparagine
Asn, N

Glutamine
Gln, Q

Threonine
Thr, T

Cysteine
Cys, C

Tyrosine
Tyr, Y

Aspartic acid
Acidic
Asp, D

Glutamic acid
Glu, E

Lysine
Basic
Lys, K

Arginine
Arg, R

Histidine
His, H

Uncommon amino acids

In addition to the 20 common amino acids, there are several uncommon ones found:

Hydroxylysine and hydroxyproline. These are found in the protein collagen. Collagen is a
fibrous protein made up of three polypeptides that form a stable assembly, but only if the
proline and lysine residues are hydroxylated. (requires vitamin C for reduction of these
amino acids to hydroxy form)

Thyroxine, an iodinated derivative of tyrosine, found in thyroglobulin (produced by

thyroid gland; requires iodine in diet)

g-carboxyglutamic acid (i.e. glutamic acid with two carboxyl groups) found in certain
blood clotting enzymes (requires vitamin K for production)

N-methyl arginine and n-acetyl lysine. Found in some DNA binding proteins known as
histones

Amino acid derivatives not found in proteins

Some amino acids are made that are not intended for incorporation into proteins, rather they
have important functionalities on their own

Serotonin (derivative of tryptophan) and g-amino butyric acid (a derivative of glutamic

acid) are both neurotransmitters

Histamine (derivative of histidine) involved in allergic response

Adrenaline (derivative of tyrosine) a hormone

Various antibiotics are amino acid derivatives (penicillin)

Acid-base Chemistry of Amino Acids

Amino acids by themselves have amino (pKa ~9.0-10.5) and carboxyl groups (pKa ~2.0-2.4)
that can be titrated

At neutral pH the amino group is protonated, and the carboxyl group is deprotonated

The side chains of acid and basic amino acids, and some polar amino acids can also be titrated:

Amino acid

Functional Group

Side chain pKa

Cysteine

-SH

8.3

Serine

-OH

13

Threonine

-OH

13

Tyrosine

-OH

10.1

Aspartic acid

-COOH

3.9

Glutamic acid

-COOH

4.3

Histidine

Imidazole ring

6.0

Arginine

Guanidino

12.5

-NH2

10.5

Lysine

Physiological pH is near neutral. It would appear that only histidine is of physiological

relevance. However, pKa values can be shifted significantly by neighboring charged
groups in complex molecular structures.

Reactions of amino acids

Free amino acids (excluding proline) share similar chemical reactivities due to the
common amino and carboxyl groups.

Different amino acid side chains have different chemical reactivities.

Therefore, reactivities of different proteins reflects the composition of the unique
sequence of amino acids in their structure.

Some common carboxyl-group reactivities:

A common side chain reaction involving cysteine:

Reference:
http://www.mikeblaber.org/oldwine/BCH4053/Lecture06/Lecture06.htm