Ionization and Chirality - Lesson 10

dipolar ions / zwitterions

in solution at pH 7, free amino acids exist as this

- NH3+ (protonated) and COO- (deprotonated)

- ionization state is zero

pH

a change in this will alter zwitterion's ionization state

how pH alters zwitterions

alters hydrogen ion concentrations within the solution

alter likelihood of functional group protonation or deprotonation

Ionic form of amino acids - Acid-base behavior of glycine

Another way to look at amino acid charged stated

pH

a measure of the hydrogen (H+) ion concentration

alpha carboxyl pKa

pKa is 2, if it is a pH above, it will lose a hydrogen

alpha amine pKa

pKA of 9, will stay protonated until you get above pH of 9, then it will lose a proton and become neutral NH2

pH calculation

__ = -log(H+)

pKa

reveals the pH cutoff for protonation of an ionizable functional group

below pKa cutoff

this means it is protonated

above pKa cutoff

this means it is deprotonated

pH below 2 on a free zwitterion

+1 charge on zwitterion

pH between 3-8 on zwitterion

no charge on zwitterion

pH above 9 on zwitterion

-1 charge on zwitterion

Lysine

the R group has a pKa of 10.8

Lysine in pH below 2

+2 charge on lysine

Lysine in pH between 9 - 10.8

no charge

Lysine in pH above 10.8

-1 charge

proteins have a net (overall) charge

_______ have a net (overall) charge

do not retain ionization states

because peptide bonds between carboxyl group of one amino acid and amine group of another, those groups (do or do not) retain ionization states

influence of ionization state on proteins

protein charge from amino acid ionizable side chains and terminal ends

(~95%)

what percent of naturally occurring proteins have a low net charge

highly charged proteins

ex. histones

positively-charged as primary structure about 24% lysine and arginine

charge enables interactions with negatively charged DNA

Acetylation and phosphorylation

these promo chromatin remodeling, as functional groups neutralize histones inherent charge and repel nucleic acid backbone

L amino acids and D amino acids

because of structure, most amino acids exist in two mirror-image form

configurational isomers

same chemical formula but differ in spatial arrangement / structure

L amino acids

interestingly, only _ amino acids are constituents of proteins

- slightly more soluble in aqueous environments

- eukaryotic enzymes preferentially recognize this isomer

chirality

most amino acids also display optical isomerism due to this

exception: glycine

chiral

asymmetric in that structure and mirror image not superimposable

chiral examples

achiral example

stereocenters

chiral molecules contain 1 or more _____________ or chiral centers

- typically a tetrahedral or asymmetric carbon atom

Left! L-isomer

L or D molecule?

Right! D-isomer

L or D molecule?

D-isomer

L-isomer

D-isomer

L or D isomer?

importance of isomers and chirality

fundamental components of receptor binding

importance of isomers and chirality - drug efficacy

isomer selection means to maximize ____ efficacy

importance of isomers and chirality - proprandolol

a blood pressure drug

isomer selection

also means to minimize undesirable effects

ex. Thalidomide is a synthetic sedative and hypnotic medication prescribed in the 1950's to treat anxiety, insomnia, and morning sickness in pregnant women