Title

Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B

Authors

Neelam Verma^{* 1}, Minakshi Mittal, Raman kumar Verma²

Affiliation

¹Department of Biotechnology, Punjabi University, Patiala. ²Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University, Patiala

Email

neelam_verma2@rediffmail.com; * Corresponding author

Article Type

Hypothesis

Date

received July 10, 2008, revised August 8, 2008; accepted September 21, 2008; published October 25, 2008

Abstract

Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors.

Keywords

drug design; docking; oxalyl aryl amino benzoic acid derivatives; PTP1B

Citation

Verma et al., Bioinformation 3(1): 83-88 (2008)

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.