Design of Y Receptor Selective and Proteolytically Stable PYY Analogues.

In recent years peptide YY (PYY) has attracted attention within the area of diabetes and obesity due to its involvement in food intake regulation and glucose homeostasis. It is well-known that PYY is rapidly cleaved by dipeptidyl peptidase-4 to the more Y receptor selective analogue PYY, which is further cleaved to the inactive analogue PYY. In order to improve the selectivity and proteolytic stability of the C-terminus, we synthesized several analogues incorporating N-methyl amino acids or β-homo amino acids and other non-natural amino acids.

Metabolic activation of carboxylic acids.

Background: Carboxylic acids constitute a large and heterogeneous class of both endogenous and xenobiotic compounds. A number of carboxylic acid drugs have been associated with adverse reactions, linked to the metabolic activation of the carboxylic acid moiety of the compounds, i.e.