topic 2 - amino acids

Question 1

intermolecular reactions

Answer 1

Many compounds synthesised during the drug discovery process are typically hydrophobic molecules. Binding sites of proteins are often also hydrophobic in character and hydrophobic interactions can form a significant contribution to drug-protein interactions

Enthalpy contributions arise from van der Waals bonding between e.g. alkyl, aryl groups and from p-p interactions between aromatic rings.

To influence biology, we need to use chemistry to influence biomolecules. This involves some kind of binding

Noncovalent interactions are more useful

Electrostatics
ion-ion
ion-dipole
dipole-dipole
Hydrogen bonding
Van der Waals forces
Hydrophobic effect

Question 2

what are amino acids?

Answer 2

Definition – bifunctional organic compounds that possess both a carboxyl (-COOH) and an amino (-NH2) group.

Alpha-amino acids (the most biologically important ones) have both of these attached to the same central carbon atom, referred to as the alpha(α)-carbon atom.

Question 3

amino acids - what does R stand for?

Answer 3

R stands for – a hydrogen atom or an organic group . This group maybe polar, non-polar, basic or acidic.

It is these R GROUPS that determine the properties of any particular amino acid.

Question 4

where do we get amino acids from?

Answer 4

Where do we get them from – Plants and microorganisms synthesise amino acids from simple inorganic molecules. Animals (this includes humans) cannot do this and obtain essential amino acids from their diet.

In humans the essential amino acids are: arginine, histidine, lysine, threonine, methionine, isoleucine, valine, phenylalanine and tryptophan.

The other amino acids needed by the human body can be synthesised from these essential amino acids.

Question 5

what is the dissociation constant and pKa?

Answer 5

A Brønsted-Lowry acid is a proton (hydrogen ion) donor. A Brønsted-Lowry base is a proton (hydrogen ion) acceptor.

The higher the Ka the stronger the acid.

The lower the pKa the stronger the acid.

The lower the Ka the weaker the acid.

The higher the pKa the weaker the acid.

pKa tells you the pH at which the molecule is 50% deprotonated

Question 6

the amino group as a base?

Answer 6

Basicity is most commonly measured by using the pKa of conjugate acid (CA):

The less acidic the conjugate acid, the more stable it is, the lower the Ka, the higher the pKa, and therefore the more basic the original base

Higher pKa of conjugate acid = more basic original base

Question 7

what is amino acid stereochemsitry?

Answer 7

All alpha-amino acids are chiral apart from glycine. They can exist as one of two enantiomers which are mirror images of each other.

The majority of natural amino acids, rotate plane polarised light to the left – they are L-amino acids.
Amino acids that rotate plane polarised light to the right are called D-amino acids. Sometimes this type of nomenclature is still used in the literature. To assign absolute stereochemistry the (S) and (R) designators are used.

Question 8

Naming enantiomers?

Answer 8

Cahn-Ingold-Prelog (CIP) rules, which results in the two mirror images being called either the R or S isomers. Unlike the old L and D nomenclature, these give absolute configurations. The CIP rules work by assigning priorities to each substituent about a carbon centre, from 1 to 4 – 1 is top priority, 4 is lowest priority.

1. The higher the atomic number of the substituent, the higher the rank
   e.g. S is higher rank than O, but lower rank than Cl.
2. If two substituents have the same rank, continue along the chains until you encounter an element of higher rank. e.g. -CH2Br is higher rank than –CH3 because Br is heavier than hydrogen, even if both start at carbon.
3. If none of the atoms connected to the competing chain(s), at the same point, has a greater atomic number: the chain bonded to the same atom multiple times has the greater priority e.g. C=O has higher priority than C-OH
4. When dealing with isotopes, the heavier isotopes have priority.

Question 9

amino acids - side chains non-polar (alkyl)

Answer 9

Alanine (Ala) ((A))

Valine (Val) ((V))

Leucine (Leu) ((L))

Isoleucine (Ile) ((I))

Question 10

Amino Acids – Side Chains non-polar

Answer 10

Methionine (Met) ((M))

Phenylalanine (Phe) ((F))

Tryptophan (Trp) ((W))

Tyrosine (Tyr) ((Y))

Question 11

amino acids - side chains polar

Answer 11

Serine (Ser) ((S))

Threonine (Thr) ((T))

Asparagine (Asn) ((N))

Glutamine (GLN) ((Q))

Question 12

amino acids - side chains charged

Answer 12

Aspartic acid (Asp) ((D))

Glutamic acid (Glu) ((E))

Arginine (Arg) ((R))

Histidine (His) ((H))

Lysine (Lys) ((K))

Question 13

amino acids - side chains special cases

Answer 13

Gylcine (Gly) ((G)) no stereochemistry

Proline (Pro) ((P))

Cysteine (Cys) ((C)) R - stereochemistry

Question 14

amino acid, isoelectric point (pl)

Answer 14

Cationic form > Zwitterionic form > anionic form
(at pH 2.0) (at pH 12.0)

Amino acids are amphoteric: they can react as either an acid or a base.

The predominate form in the equilibrium depends on the structure of the amino acid (side chain R) and the pH of the solution (pKa of the amino and the carboxylic group are influenced by the nature of the sidechain).

Isoelectric point (pI): The pH at which the amino acid exists largely in an overall neutral, Zwitterionic Form

Question 15

at what pH is an amino acid neutral? (for neutral amino acids)

Answer 15

For neutral amino acids, the pI is the average of the two pKa values

e.g. Alanine

pKa = 9.69 conj.acid
pKa = 2.34

PI = (2.34 + 9.68) / 2 = 6.01

Question 16

at what pH is the amino acid neutral ? (for acidic amino acids)

Answer 16

For acidic amino acids, the PI is the average of the two lower pKa values.

e.g. Aspartic acid

pKa = 9.60 conj acid
pKa = 3.65
pKa = 1.88

PI = (1.88 + 3.65) / 2 = 2.77

Question 17

at what pH is the amino acid neutral ( for basic amino acids)

Answer 17

For basic amino acids, the PI is the average of the two higher pKa values.

e.g. Lysine

pKa = 10.53 conj acid
pKa = 9.74
pKa = 8.95 conj acid

PI = (8.95 + 10.53) / 2 = 9.74