High affinity conformationally constrained nociceptin/orphanin FQ(1-13) amide analogues.
A series of cyclic analogues with a lactam linkage were prepared by solid phase peptide synthesis to explore possible biologically active conformation(s) of nociceptin/orphanin FQ (N/OFQ). cyclo[D-Asp(7),Lys(10)]- and cyclo[Asp (6),Lys(10)]N/OFQ(1-13)NH2 exhibit high affinity (Ki = 0.27 and 0.34 nM, respectively) and high potency in the GTPgammaS assay (EC 50 = 1.6 and 4.1 nM, respectively) at human nociceptin/orphanin FQ peptide (NOP) receptors. These analogues exhibit 2- to 3-fold higher affinity and 2- to 5-fold higher potency than the parent peptide.
Charoenchai
Laksana
L
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Baltimore, Baltimore, Maryland 21201, USA.
Wang
Hongyan
H
Wang
Jia Bei
JB
Aldrich
Jane V
JV
D000577:Amides / Q000737:chemistry*; D008968:Molecular Conformation; D018847:Opioid Peptides / Q000737:chemistry*; D011485:Protein Binding; D000097629:Nociceptin
D000577:Amides; D018847:Opioid Peptides; D000097629:Nociceptin