Peptide pharmaceutics

Question 1

Etanercept (Enbrel)

Answer 1

Fusion protein
An alpha TNF (tumour necrosis factor) antagonist
Made from the Fc region of human IgG1 and the extracellular domain of TNF receptor
Soluble, given Sc
50-100x at binding to TNFalpha
Dimeric therefore binds to two TNF alpha molecules
Fc region prolongs half life

Question 2

Insulin

Answer 2

Found as monomer at low conc and as dimer at high conc

Binding at B24-26 AND 28-29 important for dimerisation and binding to IR

Question 3

Modifying insulin

Answer 3

Will form hexamers in presence of Zn
As excipients in formulation can change conformers of insulin
Hexamers form straight after Sc admin but must dissociate for absorption

Question 4

Insulin analogue mods

Answer 4

Long acting- Promotes hexamer formation and plasma protein binding reduces solubility
Short acting- reduces formation of dimers/hexamers, ^ solubility

Question 5

Degludec

Answer 5

Basal human insulin with t1/2 >25hrs
C16 chain promotes formation of multihexamers once injected
Long t1/2= low fluctuations in blood glucose and effects last for >42hrs

Question 6

PEGylation

Answer 6

the addition of polyethylene glycol chains to proteins means there is less clearance and cannot get past the BBB