Synthesis and biological activity of new series of N-modified analogues of the N/OFQ(1-13)NH2 with aminophosphonate moiety

摘要

New series of N-modified analogues of the N/OFQ(1-13)NH2 with aminophosphonate moiety have been synthesized and investigated for biological activity. These peptides were prepared by solid-phase peptide synthesis—Fmoc-strategy. The N/OFQ(1-13)NH2 analogues were tested for agonistic activity in vitro on electrically stimulated rat vas deferens smooth-muscle preparations isolated from Wistar albino rats. Our study has shown that the selectivity of the peptides containing l-[(methoxy-phosphono)methylamino]cycloalkanecarboxylic acids to the N-side of Phe is not changed—they remain selective agonists of NOP receptors. The derivative with the largest ring (NOC-6) demonstrated efficacy similar to that of N/OFQ(1-13)NH2, but in a 10-fold higher concentration. The agonistic activity of newly synthesized N-modified analogues of N/OFQ(1-13)NH2 with aminophosphonate moiety was investigated for the first time.