Lipolytic activities of stereoisomeric pentapeptides related to the partial structure of ACTH.

Lipolytic activities of eight stereoisomers of pentapeptide, histidyl-phenylalanylarginyl-tryptophyiglycine, corresponding to the positions 6•`10 in the NH2-terminal portion of ACTH were assayed in vitro. All the isomers were active in the experiment using rat epididymal fat. However, three isomers, all-D, L-His-L-Phe-L-Arg-D-Trp-Gly, and D-His-D-Phe-D-Arg-L-Trp-Gly, were inactive in rabbit perirenal fat at the dosage of 1 mg per fat pad. No definite correlation between the replacement of constituent L-amino acid residue (s) with corresponding D-amino acid residue(s) and the alteration of lipolytic activity was found. Lipolytic activity of all-L peptide was completely destroyed when heated with dilute alkali. All-D and D-His-L-Phe-L-Arg-L-Trp-Gly did not alter lipolysis elicited by ACTH in both rabbit and rat fats. These biological patterns of lipolytic activities of stereoisomeric pentapeptides were not parallel with their MSH activities, suggesting that peptide has different sites of activity and different stereospecificities in each activity. The tetrapeptide, His-Phe-Arg-Trp, was also proposed as a minimal structure for lipolytic activity in the partial structure of ACTH.