Lecture 6 - Peptide and Protein Therapeutics 2

Question 1

Why are protein modifications carried out?

Answer 1

Improve stability, efficacy and PK

Question 2

How are proteins modified?

Answer 2

Engineered using recombinant DNA technology or by chemical modification of the protein

for example
- fusion proteins
- antibody-drug complexes
- humanisation of mAbs
- modified insulins

Question 3

How do we reduce immunogenicity of monoclonal antibodies?

Answer 3

We humanise them - take the antigen recognition site from the antibody that’s raised in mouse and fuse that with the human immunoglobulin to give the chimeric monoclonal antibody
we can fully humanise

Question 4

Describe the protein modifications in insulin

Answer 4

Monomer only at low concentrations
Dimer at higher concentrations
B24-B26 and B28-B29 crucial for dimerisation and binding to IR