[1] The current highest selling marketed diabetic drug Liraglutide, incorporates a lipid chain to extend plasma circulation and prolong bioavailability.
This is due to the palmitoyl chain allowing non covalent binding to albumin, which delays proteolytic attack by DPP IV and also rapid renal clearance.
[8] When dense-core vesicles are triggered, they release the stored information into the blood or extracellular space,[9] resulting in amyloid disassembly, in order for action.
Many strategies have been employed to increase the stability of peptide drugs, because although they have so many desirable characteristics, they are short lived in the body as a result of rapid degradation and clearance.
Advantages of this technique include increased metabolic stability, and facilitated transport across cell membranes, although of the most favourable aspects is their ability to promote oral absorption.
[17] Peptides have a very low oral availability (less than 1-2%),[18][19][20] as a result of insufficient absorption and rapid degradation and clearance, thus making this method an attractive one.
[17] Cyclization can also be used as a method to decrease proteolytic degradation and prolong half-life, to make the peptide conformation more rigid to hinder enzymatic cleavage.
Human serum albumin is the most abundant plasma protein with a molecular weight of 66.4 kDa,[24] and it is involved in many essential bodily functions to maintain homeostasis.
Serum albumin has an extraordinary long half-life of 2–4 weeks which is much longer than other plasma proteins,[25] due to it binding to the neonatal Fc receptor (FcRn).
Studies on a lipidated analogue of insulin, detemir, revealed a prolonged action as a result of its affinity for human serum albumin.
The reduction in activity from PEGylation compared to lipidation is due to the loss of receptor affinity, and it is suggested that this is because of its increased molecular weight which causes steric hindrance.