PY5010 Amino Acids, Peptides and Proteins

★ Amino acids
○ Most naturally-occurring amino acids are alpha amino acids
○ AAs may be linked via amide bonds to give peptides (<50) or proteins (>50)
■ They may have specific biological activities and may be administered
as drugs
○ Synthetic AAs/peptides may be produced with specific activities
○ Gamma-aminobutyric acid (GABA) is a naturally-occurring amino acid
synthesised in the body from glutamic acid
■ Predominant inhibitory NT in the brain
○ GABAA receptors are on Cl- ion channels
■ GABAB receptors are GPCRs

★ Amino acid synthesis

○ Alpha AAs may be synthesised in two ways
■ Hell-Vollhardt Zelinski reaction
■ Strecker synthesis
■ Both produce racemixes unless chiral auxiliaries are used
● Racemates require resolution to obtain optically pure AAs
○ Strecker synthesis
■ Reaction of CN with iminium ion

■ NH4Cl is a source of NH3

■ Hydrolysis then provides the AA:

○ Asymmetric Strecker synthesis

○ Hell-Vollhardt Zelinski reaction

 ■ Involves alpha bromination of a carboxylic acid followed by
displacement of the halogen by ammonia

○ Resolution of racemic AAs via enzymes

■ First step is N-acylation

■ Second step is reaction with carboxypeptidase (CBPA)

■ Only the peptide bond of the S enantiomer is cleaved by the enzyme

and may be separated from the R isomer by formation of the
water-soluble salt
★ Peptides
○ Enkephalins contain 5 AAs
■ Naturally-occurring peptides acting as potent painkillers
■ Bond to opioid family of receptors
■ Released by neurons in CNS
○ Cyclic peptides
■ Ends of peptide chain may be linked to form a ring
■ Gramicidin S is an antibiotic effective against some bacteria and fungi
● Contains 10 AAs
○ Glutathione
■ Tripeptide present in nearly all body tissues
■ Functions to remove dangerous oxidising agents from the body
■ Role is in detoxification
● E.g. paracetamol overdose
● Normally paracetamol is metabolised to a hydrolamine before
excretion

○ Glutathione detoxifies this oxidised metabolite to form a

stable derivative

● Under normal consumption of paracetamol there is sufficient

glutathione for detox
○ One molecule of glutathione is consumed for every
paracetamol molecule (1:1 ratio)
○ In an OD situation the normal supply of glutathione is
quickly depleted
○ The liver suffers severe damage due to the reactive
paracetamol metabolite
○ Tablet formulations have been made to include
paracetamol with acetylcysteine or methionine