Modification of Peptides to Limit Metabolism

Naturally occurring endogenous peptide neurotransmitters and other peptides have had limited usage as drugs due to the rapid proteolysis in vivo. Rapid proteolysis of peptides by proteolytic enzymes can occur for many reasons and can be beneficial or non-beneficial depending upon the biological circumstances. If the metabolic stability of the peptides is a desired property, however, the pharmacophore residues of the endogenous hormone and neurotransmitter peptides which are essential for the biological activities need to be identified, and then protected from rapid proteolysis. In addition, proteolytic action and its specificity on metabolically unstable desired peptides needs to be further established in order to provide a better framework for designing metabolically stabilized peptides. We have systematically described some approaches which have been taken to stabilize peptides from proteolytic action.