Potent tetrapeptide enkephalins |
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Authors: | Richard E Chipkin Dan H Morris Michael G English James D Rosamond Charles H Stammer Eunice J York John M Stewart |
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Institution: | 1. Department of Biochemistry, University of Colorado School of Medicine, Denver, Colorado, 80262, USA;7. University of Georgia, Athens, Georgia, 30602, USA;71. Pennwalt Pharmaceutical Division, Rochester, New York, 14603, USA |
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Abstract: | Small peptides with opiate-like activity have generally had structures closely resembling that of the opioid pentapeptide enkephalin: Tyr-Gly-Gly-Phe-Met-COOH. Single deletions of any one of the amino acids has been demonstrated to reduce opiate activity drastically. In this work we show that the potency losses resulting from the removal of glycine3 can be fully attenuated by substitution of D-alanine in position two and derivatization of the acid to the amide. This tetrapeptide (Tyr-DAla-Phe-Met-NH2) has narcotic activity similar to the parent pentapeptide in the guinea pig ileum and mouse tail-flick tests. This enhanced potency, relative to the unaltered tetrapeptide, is theorized to arise from increased resistance to enzymatic destruction. the data presented show that a five amino acid sequence is not mandatory for the expression of opiate activity in enkephalin analogs. |
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