A super active cyclic hexapeptide analog of somatostatin
| Autor: | William J. Paleveda, Roger M. Freidinger, Hoff Dale R, Ruth F. Nutt, L. D. Hall, Stephen F. Brady, Lawrence J. Mandarino, Hirschmann Ralph F, Dominick J. Tocco, Paul S. Anderson, Richard L. Vandlen, Anthony G. Zacchei, Richard Saperstein, Paul E. Curley, John E. Gerich, Debra S. Perlow, Eugene H. Cordes, Daniel F. Veber, C. Dylion Colton |
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| Rok vydání: | 1984 |
| Předmět: |
Blood Glucose
medicine.medical_specialty medicine.medical_treatment In Vitro Techniques Peptide hormone Biology Peptides Cyclic Glucagon General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Mice Structure-Activity Relationship Dogs Internal medicine Insulin Secretion medicine Animals Insulin Potency Structure–activity relationship General Pharmacology Toxicology and Pharmaceutics Biological activity General Medicine Rats Postprandial Somatostatin Endocrinology Growth Hormone Hyperglycemia Oligopeptides |
| Zdroj: | Life Sciences. 34:1371-1378 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(84)90009-2 |
| Popis: | The cyclic hexapeptide, cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe), I, has been shown to have the biological properties of somatostatin. We now report structure-activity studies which optimize the potency of this cyclic hexapeptide series with the synthesis of cyclo (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), II, which is 50-100 times more potent than somatostatin for the inhibition of insulin, glucagon and growth hormone release. The hydroxyl group of tyrosine is seen to lend a 10-fold enhancement to the potency. Potency also is found to be correlated with hydrophobicity. II is found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The analog is found to be quite stable in the blood and in the gastrointestinal tract, but the bioavailability after oral administration is only 1-3%. The biological properties and long duration of II should allow clinical evaluation of the inhibition of glucagon release as an adjunct to insulin in the treatment of patients with diabetes. |
| Databáze: | OpenAIRE |
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