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Synthesis and biological activity of novel small peptides with aminophosphonates moiety as NOP receptor ligands

Amino Acids, ISSN: 0939-4451, Vol: 39, Issue: 5, Page: 1537-1543
2010
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Article Description

The aim of the present study was the synthesis and the biological screening of new analogs of Ac-RYYRWK-NH, modified at the N-terminal with 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids. The four newly synthesized ligands for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) have been prepared by solid-phase peptide synthesis-Fmoc-strategy. These compounds were tested for agonistic activity in vitro on electrically stimulated smooth-muscle preparations isolated from vas deferens of Wistar rats. Our data showed that substitution of Arg at position 1 with aminophosphonates moiety decreased significantly the affinity of ligands to the NOP receptor. Furthermore, the enlargement of the cycle (with 5-8 carbon atoms) additionally diminished both the activity and the selectivity for NOP-receptor. © 2010 Springer-Verlag.

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