Research Article Open Access

Pharmacophore Pattern Identification of Tachykinin Receptor Selective Peptide Agonists: Implications in Receptor Selectivity

Anjali Dike1, Indu R. Chandrashekaran2, Anil K. Mantha3, Najma Z. Baquer4 and Sudha M. Cowsik4
  • 1 Jawaharlal Nehru University, India
  • 2 The Walter and Eliza Hall Institute of Medical Research, United States
  • 3 University of Texas Medical Branch Galveston, United States
  • 4 Washington University School of Medicine, United States

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.

American Journal of Biochemistry and Biotechnology
Volume 3 No. 4, 2007, 180-186

DOI: https://doi.org/10.3844/ajbbsp.2007.180.186

Submitted On: 12 February 2007 Published On: 31 December 2007

How to Cite: Dike, A., Chandrashekaran, I. R., Mantha, A. K., Baquer, N. Z. & Cowsik, S. M. (2007). Pharmacophore Pattern Identification of Tachykinin Receptor Selective Peptide Agonists: Implications in Receptor Selectivity. American Journal of Biochemistry and Biotechnology, 3(4), 180-186. https://doi.org/10.3844/ajbbsp.2007.180.186

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Keywords

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