title: Targeting PKC-β II by Peptides and Peptidomimetics Derived from RACK 1: An In Silico Approach.
abstract: Diabetes causes contractile myocardial dysfunction through accelerated atherosclerosis and hypertension, termed Diabetic Cardiomyopathy. Experimental results reveals liaison between cardiovascular disease and diabetic complications. Protein kinase C (PKC), a heterogeneous family of phospholipid dependent kinases was found to be specifically involved in diabetic complications, of which PKC-β II isoform played a significant role in induction of this fatal disease. Members of PKC family share high degree of similarity in both structure and functions, which has given rise to specificity related issues. In the present study, we have designed peptides and peptidomimetics based on RACK 1 (Receptor for Activated C Kinases) region, as this protein increases the substrate phosphorylation and stabilizes the activated form of PKC-β II. RACK 1 being specific for PKC-β II could resolve the specificity issue and also peptides and peptidomimetics, being conformationally restrained structures offers potential advantages of being used as drug molecules over organic molecules. This study has provided useful insights that may contribute to the development of molecules which may be useful in the treatment of diabetic complications.
authors.affiliation: Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab - 160 062, India phone: +91-172-221468286-2025; fax: +91-172-2214692.
authors.forename: Kapil
authors.initials: K
authors.lastname: Jain
authors.affiliation: Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab - 160 062, India phone: +91-172-221468286-2025; fax: +91-172-2214692. mesophia@niper.ac.in.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
keywords: Diabetic Cardiomyopathy; Peptides; Peptidomimetics; Protein kinase C; RACK 1; docking