Impact of Osmolytes in Conformational Modulation of Protein and Its Applications in Biotechnology

Cells utilize small molecules osmolytes to defend themselves from the stressed environmental conditions. These osmolytes protect the cells by stabilizing the protein against misfolded or aggregated conformation. This is important because aggregation, misf

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Impact of Osmolytes in Conformational Modulation of Protein and Its Applications in Biotechnology Tajalli Ilm Chandel, Mohsin Vahid Khan, and Rizwan Hasan Khan

Contents 7.1  Introduction 7.1.1  Protein Misfolding, Aggregation and Conformational Diseases 7.1.2  Naturally Occurring Osmolytes 7.2  Action of Osmolytes on Protein 7.2.1  Role of Gibbs Free Energy of Preferential Exclusion 7.2.2  Role of Surface Tension in Protein Folding 7.2.3  Osmolytes as Inhibitors of Protein Misfolding and Aggregation 7.3  Applications of Osmolytes in Biotechnology 7.3.1  PCR Amplification 7.3.2  Use in Pharmaceuticals 7.3.3  Osmolytes as Chemical Chaperones 7.3.4  Generation of Stress Resistant Transgenic Organisms 7.3.5  Uses in Cosmeceuticals 7.3.6  Osmolytes as Cryoprotectant 7.3.7  Health 7.4  Summary and Future Perspectives References

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T.I. Chandel • M.V. Khan • R.H. Khan (*) Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India e-mail: [email protected], [email protected] © Springer Nature Singapore Pte Ltd. 2017 L. Rajendrakumar Singh, T.A. Dar (eds.), Cellular Osmolytes, DOI 10.1007/978-981-10-3707-8_7

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Abstract

Cells utilize small molecules osmolytes to defend themselves from the stressed environmental conditions. These osmolytes protect the cells by stabilizing the protein against misfolded or aggregated conformation. This is important because aggregation, misfolding and destabilization of the protein lead to several life-­threatening neurodegenerative disorders. So, we have thrown light on some of the properties of the osmolyte which assist in protein folding, increases their stability and inhibit aggregation. Osmolytes are also known as chemical chaperones. Hence, it may be therapeutically used for several misfolding diseases. The present chapter discusses the impact of these small molecules on folding of proteins and their stabilization. Keywords

Protein folding • Osmophobicity • Gibbs free energy • Preferential exclusion • Surface tension

Abbreviation CFTR Cystic fibrosis transmembrane conductance regulator

7.1

Introduction

Aggregation of protein is one of the most interesting topics in protein world. The reasons for the development of interest in this area have arisen due to some facts, i.e. the knowledge of the molecular basis of the aggregation of the protein may assist to gain deeper insight into the physicochemical features of protein folding; it also provides information on the pathological conditions of the protein misfolding resulting in conformational diseases or neurodegenerative diseases such as Parkinson’s, type II diabetes, Alzheimer’s, cystic fibrosis, some forms of emphysema, etc.(Stefani 2004).

7.1.1 P  rotein Misfolding, Aggregation and Conformational Diseases The most stable form of the protein at physiological pH is the native conformation. The three dimensional structure of the protein is respons