Conformational rigidity versus flexibility in a novel peptidic neurokinin A receptor antagonist.

Abstract

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.

• Authors: V Pavone, A Lombardi, C A Maggi, L Quartara, C Pedone
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) 1995 Jul-Aug Vol. 1 Issue 4 Pg. 236-40 ISSN: 1075-2617 [Print] England
• PMID: 9223001 (Publication Type: Journal Article)

Chemical References

• Peptides, Cyclic
• Receptors, Neurokinin-2
• cyclo(Gln-Trp-Phe-Gly-Leu-Met)
• MEN 10627

Topics

• Amino Acid Sequence
• Animals
• Cricetinae
• Drug Design
• Guinea Pigs
• In Vitro Techniques
• Male
• Molecular Structure
• Muscle, Smooth (drug effects)
• Peptides, Cyclic (chemical synthesis, chemistry, pharmacology)
• Protein Conformation
• Rabbits
• Rats
• Receptors, Neurokinin-2 (antagonists & inhibitors)
• Structure-Activity Relationship
• Urinary Bladder (drug effects)