Synthesis and biological activity of the first cyclic biphalin analogues.
Biphalin is a linear octapeptide with strong opioid activity. Its structure is based on two identical sequences derived from enkephalins joined C-terminal to C-terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH<--Phe<--Gly<--D-Ala<--Tyr). In this study we present the design, synthesis, and biological evaluation of the first cyclic biphalin analogues. d-Alanine residues in positions 2, 2' of the parent peptide were replaced by d- and l-cysteine and an intramolecular disulfide bond between the cysteine thiol groups was introduced. We obtained two cyclic analogues with quite different biological profiles.
Mollica
Adriano
A
Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
Davis
Peg
P
Ma
Shou-Wu
SW
Porreca
Frank
F
Lai
Josephine
J
Hruby
Victor J
VJ
D001665:Binding Sites; D003500:Cyclization; D004745:Enkephalins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013329:Structure-Activity Relationship
D004745:Enkephalins; D008024:Ligands; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C053673:biphalin