Abstract
A novel N-terminal-to-side chain cyclic dynorphin A analogue lacking the basic N-terminus was designed based on Ac[Lys2,Trp3,Trp4,D-Ala8] dynorphin A-(1-11)NH2 (Wan et al. J. Med. Chem. 1999, 42, 3011-3013). cycloN,5- [Trp3,Trp4, Glu5]dynorphin A-(1-11)NH2 showed similar κ opioid receptor affinity (Ki = 27 nM) and selectivity (Ki ratio (κ/μ/δ) = 1/12/330) to the linear peptide and antagonized dynorphin A-(1-13)NH2 at κ opioid receptors. This is the first opioid peptide cyclized through the N-terminus that retains high opioid receptor affinity.