A novel N-terminal cyclic dynorphin A analogue cyclo(N,5)[Trp(3),Trp(4),Glu(5)] dynorphin A-(1-11)NH(2) that lacks the basic N-terminus.
A novel N-terminal-to-side chain cyclic dynorphin A analogue lacking the basic N-terminus was designed based on Ac[Lys(2),Trp(3),Trp(4),d-Ala(8)]dynorphin A-(1-11)NH(2) (Wan et al. J. Med. Chem. 1999, 42, 3011-3013). cyclo(N,5)[Trp(3),Trp(4),Glu(5)]dynorphin A-(1-11)NH(2) showed similar kappa opioid receptor affinity (K(i) = 27 nM) and selectivity (K(i) ratio (kappa/mu/delta) = 1/12/330) to the linear peptide and antagonized dynorphin A-(1-13)NH(2) at kappa opioid receptors. This is the first opioid peptide cyclized through the N-terminus that retains high opioid receptor affinity.
Vig
Balvinder S
BS
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
Murray
Thomas F
TF
Aldrich
Jane V
JV
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004399:Dynorphins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*
D008024:Ligands; D010456:Peptides, Cyclic; D017473:Receptors, Opioid, kappa; C473669:dynorphin A-(1-11)amide, cyclo(N,5)(Trp(3)-Trp(4)-Glu(5))--; D004399:Dynorphins; D000242:Cyclic AMP