Pharmacophore pattern identification of tachykinin receptor selective peptide agonists: Implications in receptor selectivity

Anjali Dike, Indu R. Chandrashekaran, Anil K. Mantha, Najma Z. Baquer, Sudha M. Cowsik

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The mammalian tachykinin (TK) peptides and their three Neurokinin (NK1, NK2 and NK3) receptors represent an effector system with wide-ranging actions on neuronal, airway smooth muscle, mucosal, endothelial, immune, inflammatory and remodeling cell function. Recent clinical and preclinical data suggests the pathophysiological role of TKs in various diseases including asthma, emesis and depression. The TK-NK receptor interactions and overlapping functions mediated by each NK receptor indicate added therapeutic benefit of using multiple NK receptor blockade. In the absence of structural data on neurokinin receptors, the membrane-induced structure of tachykinins play an important role as a first step towards understanding structure-activity relationship. A comparison of the conformational features of different NK1, NK2 and NK3 receptor agonists highlights several features which might be responsible for determining selectivity for the particular receptor subtype. An attempt has been made to correlate the observed conformational differences to the binding ability and biological activity of various NK1, NK2 and NK3 receptor agonists. The membrane bound conformations of tachykinins have been used as a starting point, leading to useful pharmacophore patterns that can be used for identifying lead structures with novel scaffolds.

Original languageEnglish
Pages (from-to)180-186
Number of pages7
JournalAmerican Journal of Biochemistry and Biotechnology
Volume3
Issue number4
DOIs
StatePublished - Jan 1 2007

Keywords

  • Neurokinin receptor
  • Neuropeptide
  • Pharmacophore pattern
  • Solution conformation
  • Tachykinin

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