SYNTHESIS AND IN-VITRO STUDY OF A DIGLYCERIDE PRODRUG OF A PEPTIDE

A diglyceride derivative of a pentapeptide renin inhibitor, the almito yl-[Iva-Phe-Nle-Sta-Ala-Sta-acetyl]-glycerol was synthesized and teste d in vitro as a potential prodrug for oral administration. The ability of the diglyceride analog to inhibit the renin activity was equivalen t to that of the parent peptide after predigestion with pancreatic lip ase. Furthermore, the presence of the palmitoyl groups was found to in duce, in vitro, an efficient protection of the peptide from gastric an d intestinal hydrolysis. During incubation with intestinal and gastric fluids, and with alpha-chymotrypsin and pancreatic lipase, the glycer olipidic derivative was more stable than the peptide alone. These resu lts support the use of glycerolipidic prodrug for oral administration of peptides.