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World J Biol Chem. Mar 26, 2011; 2(3): 39-47
Published online Mar 26, 2011. doi: 10.4331/wjbc.v2.i3.39
Allosteric inhibitors of plasma membrane Ca2+ pumps: Invention and applications of caloxins
Jyoti Pande, Magdalena M Szewczyk, Ashok K Grover
Jyoti Pande, Ashok K Grover, Department of Medicine, HSC 4N41, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
Magdalena M Szewczyk, Ashok K Grover, Department of Biology, HSC 4N41, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
Author contributions: Pande J, Grover AK and Szewczyk MM made 50%, 30% and 20% contributions, respectively.
Supported by Grant-in-Aid from the Heart and Stroke Foundation of Ontario and a Doctoral Award to MMS from the Heart and Stroke Foundation of Canada; This work is part of a pending patent and US Patent 7091174B2
Correspondence to: Dr. Ashok K Grover, Department of Medicine, HSC 4N41, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. groverak@mcmaster.ca
Telephone: +1-905-5259140 Fax: +1-905-5223114
Received: October 8, 2010
Revised: November 18, 2010
Accepted: November 25, 2010
Published online: March 26, 2011
Abstract

Plasma membrane Ca2+ pumps (PMCA) play a major role in Ca2+ homeostasis and signaling by extruding cellular Ca2+ with high affinity. PMCA isoforms are encoded by four genes which are expressed differentially in various cell types in normal and disease states. Therefore, PMCA isoform selective inhibitors would aid in delineating their role in physiology and pathophysiology. We are testing the hypothesis that extracellular domains of PMCA can be used as allosteric targets to obtain a novel class of PMCA-specific inhibitors termed caloxins. This review presents the concepts behind the invention of caloxins and our progress in this area. A section is also devoted to the applications of caloxins in literature. We anticipate that isoform-selective caloxins will aid in understanding PMCA physiology in health and disease. With strategies to develop therapeutics from bioactive peptides, caloxins may become clinically useful in cardiovascular diseases, neurological disorders, retinopathy, cancer and contraception.

Keywords: Phage display; Calcium signaling; Plasma membrane Ca2+ pumps; Hypertension; Neuronal disorders; Contraception; Cancer; Thrombosis; Lipid rafts