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

J Med Chem. 2003 Apr 10;46(8):1279-82. doi: 10.1021/jm0256023.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / biosynthesis
  • Dynorphins / chemical synthesis*
  • Dynorphins / chemistry
  • Dynorphins / pharmacology
  • Ligands
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Receptors, Opioid, kappa / antagonists & inhibitors*

Substances

  • Ligands
  • Peptides, Cyclic
  • Receptors, Opioid, kappa
  • dynorphin A-(1-11)amide, cyclo(N,5)(Trp(3)-Trp(4)-Glu(5))--
  • Dynorphins
  • Cyclic AMP