SYNTHESIS AND CHANGES IN AFFINITY OF NOVEL TRYPTOPHAN HEXAPEPTIDE ANALOGS
E. Naydenova, . Zamfirova, N. Pavlov, P. Todorov, P. Mateeva, J. Martinez and M. Calmès
Department of Organic Chemistry, UCTM, Bulgaria.
Abstract:
The numerous endogenous opioid peptides exert their effects through the activation of μ, δ, к and ε opioid receptors. Nociceptin is a neuropeptide capable of inducing a variety of biological actions via activation of a specific G-protein coupled receptor. This new NOP receptor system belongs to the opioid family. Both receptor-specific opioid agonists and antagonists are useful pharmacological tools and have potential as therapeutic agents.
The aim of the present study was the synthesis and the biological screening of new analogues of Ac-RFMWMK-NH2 and Ac-RYYRWK-NH2, modified in position 4 and 5 respectively with newly synthesized β2-tryptophan analogues. The biological activity (EC50 and Emax) of the compounds were tested on electrically stimulated preparations of rat vas deferens. We have found that the replacement of Trp whit different β2-tryptophane analogues modified the selectivity of the peptides.
Acknowledgments: The research was supported by Grant DTK 02/61 of the National Research Fund, Bulgaria.
Keywords: NOP receptor analogs, Hexapeptides, β2-tryptophane analogues and Rat vas deferens