Synthesis and in vitro study of a diglyceride prodrug of a peptide

A diglyceride derivative of a pentapeptide renin inhibitor, the 1,3-dipalmitoyl-[Iva-Phe-Nle-Sta-Ala-Sta-acetyl]-glycerol was synthesized and tested in vitro as a potential prodrug for oral administration. The ability of the diglyceride analog to inhibit the renin activity was equivalent to that of...

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Bibliographic Details
Published in:Pharmaceutical research 1994-08, Vol.11 (8), p.1082-1087
Main Authors: DELIE, F, COUVREUR, P, NISATO, D, MICHEL, J.-B, PUISIEUX, F, LETOURNEUX, Y
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biological and medical sciences
Buffers
Cesium
Chemical Phenomena
Chemistry, Physical
Diglycerides - chemical synthesis
General pharmacology
Humans
Hydrolysis
In Vitro Techniques
Lipase
Medical sciences
Molecular Sequence Data
Oligopeptides - chemical synthesis
Peptides - chemical synthesis
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Prodrugs - chemical synthesis
Renin - antagonists & inhibitors
Solubility
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Summary:A diglyceride derivative of a pentapeptide renin inhibitor, the 1,3-dipalmitoyl-[Iva-Phe-Nle-Sta-Ala-Sta-acetyl]-glycerol was synthesized and tested in vitro as a potential prodrug for oral administration. The ability of the diglyceride analog to inhibit the renin activity was equivalent to that of the parent peptide after predigestion with pancreatic lipase. Furthermore, the presence of the palmitoyl groups was found to induce, in vitro, an efficient protection of the peptide from gastric and intestinal hydrolysis. During incubation with intestinal and gastric fluids, and with alpha-chymotrypsin and pancreatic lipase, the glycerolipidic derivative was more stable than the peptide alone. These results support the use of glycerolipidic prodrug for oral administration of peptides.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1018916311111