Conformational rigidity versus flexibility in a novel peptidic neurokinin A receptor antagonist.
Neurokinin A receptor antagonists have been proposed as a new class of drugs for several applications in humans (asthma, intestinal motility, etc.). The rational design, synthesis, structural characterization and biological activity evaluation of a new potent, highly selective, long-lasting, peptide-based receptor antagonist are reported. The structure-activity relationship indicates that the conformational rigidity determines potency, specificity and especially the long life of the molecule in the living body. MEN10627 is the prototype of a new class of cyclic, peptide-based, neurokinin A receptor antagonists and it is a suitable candidate for clinical testing in humans.
Pavone
V
V
Department of Chemistry, University of Napoli, Italy.
Lombardi
A
A
Maggi
C A
CA
Quartara
L
L
Pedone
C
C
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D015195:Drug Design; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects
D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C090951:MEN 10627