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

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Abstract

The aim of the present study was the synthesis and the biological screening of new analogs of Ac-RYYRWK-NH2, 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.

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Acknowledgments

This study was supported by Grant DTK_02/61 of the National Research Fund, Bulgaria.

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Authors and Affiliations

  1. Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756, Sofia, Bulgaria

    Emilia D. Naydenova, Petar T. Todorov & Nikola D. Pavlov

  2. Institute of Neurobiology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Polina I. Mateeva, Rositza N. Zamfirova & Simeon B. Todorov

Authors
  1. Emilia D. Naydenova
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  2. Petar T. Todorov
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  3. Polina I. Mateeva
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  4. Rositza N. Zamfirova
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  5. Nikola D. Pavlov
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  6. Simeon B. Todorov
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Correspondence to Emilia D. Naydenova.

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Naydenova, E.D., Todorov, P.T., Mateeva, P.I. et al. Synthesis and biological activity of novel small peptides with aminophosphonates moiety as NOP receptor ligands. Amino Acids 39, 1537–1543 (2010). https://doi.org/10.1007/s00726-010-0624-1

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  • DOI: https://doi.org/10.1007/s00726-010-0624-1

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