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From peptides to peptidomimetics: rational design of potential PKC-β II inhibitors

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Abstract

Chronic hyperglycaemia is a major initiator of diabetic cardiovascular complications and microvascular complications such as retinopathy, neuropathy and nephropathy. Experimental results reveal liaison between cardiovascular disease and diabetic complications. Of the various targets, PKCs were identified to be specifically involved in diabetic complications, of which PKCβII isoform was found to play a significant role. Although the benefit of PKCβII is immense, not a single molecule has been approved yet for diabetic treatment. Because protein kinases share a high degree of similarity in both structure and functions, developing a highly specific inhibitor has been a challenging task. In this study, we have designed peptidomimetics based on autoinhibitory domain as this domain has a recognition motif specific for each isoform to resolve the specificity issue and validated the designed peptidomimetics by molecular docking. This study has provided useful insights into molecules that may be useful for diabetic complications.

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Acknowledgments

The authors thank the Department of Science and Technology (DST) and Council of Scientific and Industrial Research (CSIR) New Delhi for financial assistance.

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Correspondence to M. Elizabeth Sobhia.

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Divya, P.S., Jain, K. & Sobhia, M.E. From peptides to peptidomimetics: rational design of potential PKC-β II inhibitors. Med Chem Res 22, 625–634 (2013). https://doi.org/10.1007/s00044-012-0056-4

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  • DOI: https://doi.org/10.1007/s00044-012-0056-4

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