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

• Published in: Amino acids 2012-09, Vol.43 (3), p.1217-1223
• Main Authors: Todorov, Petar T., Mateeva, Polina I., Zamfirova, Rositza N., Pavlov, Nikola D., Naydenova, Emilia D.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical Chemistry; Animals; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Electric Stimulation; In Vitro Techniques; Life Sciences; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Neurobiology; Nociceptin; Nociceptin Receptor; Opioid Peptides - chemical synthesis; Opioid Peptides - pharmacology; Organophosphonates - chemical synthesis; Organophosphonates - pharmacology; Original Article; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Proteomics; Rats; Rats, Wistar; Receptors, Opioid - agonists; Structure-Activity Relationship; Vas Deferens - drug effects; Vas Deferens - physiology
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-011-1177-7

New series of N-modified analogues of the N/OFQ(1–13)NH 2 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)NH 2 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)NH 2 , but in a 10-fold higher concentration. The agonistic activity of newly synthesized N-modified analogues of N/OFQ(1–13)NH 2 with aminophosphonate moiety was investigated for the first time.