Synthesis and biological activity of new series of N-modified analogues of the N/OFQ(1-3)NH2 with aminophosphonate moiety

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• 作者：Petar T. Todorov (1)
  Polina I. Mateeva (2)
  Rositza N. Zamfirova (2)
  Nikola D. Pavlov (1)
  Emilia D. Naydenova (1) e_naydenova@abv.bg
• 关键词：Nociceptin analogues – Nociceptin/orphanin FQ – NOP receptor – SPPS – Aminophosphonates – Rat vas deferens
• 刊名：Amino Acids
• 出版年：2012
• 出版时间：September 2012
• 年：2012
• 卷：43
• 期：3
• 页码：1217-1223
• 全文大小：577.2 KB
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• 作者单位：1. Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria2. Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
• ISSN：1438-2199

文摘

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 1-[(methoxyphosphono)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.