Surface Plasmon Resonance Studies Resolve the Enigmatic Endotoxin Neutralizing Activity of Polymyxin B

Thomas, Celestine J and Surolia, Namita and Surolia, Avadhesha (1999) Surface Plasmon Resonance Studies Resolve the Enigmatic Endotoxin Neutralizing Activity of Polymyxin B. In: The Journal of Biological Chemistry, 274 (42). pp. 29624-29627.

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Abstract

Polymyxin B (PMB), a cyclic cationic peptide antibiotic, despite its severe side effects continues to occupy a premiere position for treating endotoxicosis. Its mode of neutralization of endotoxin has remained elusive for the last three decades. Several synthetic peptide mimics of PMB, capable of binding endotoxin, have been made. However, the binding ability alone appears to be a deceptive indicator of endotoxin neutralizing activity as molecules with similar binding propensities could either sequester or opsonize the toxin. Hence identification of additional physical parameters which describe adequately the outcome of PMB-endotoxin interaction become imperative. Surface plasmon resonance (SPR) studies reported here show that several mimics of PMB despite exhibiting lipopolysaccharide binding affinities comparable with it but, unlike it, do not sequester the endotoxin. These studies thus provide a striking illustration of the difference in the behavior of PMB, vis a vis its mimics toward the endotoxin lamellae, and define further, in chemical terms, mechanism of the action of PMB and allow us to posit that the design of molecules as effective antidotes for sepsis should incorporate the ability to sequester endotoxin specifically.

Item Type:	Journal Article
Publication:	The Journal of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology
Additional Information:	Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
Keywords:	Biochemistry;Molecular-Biophysics;Toxicology
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	27 Sep 2007
Last Modified:	19 Sep 2010 04:39
URI:	http://eprints.iisc.ac.in/id/eprint/11927

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