title: Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.
abstract: We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Kalina Campus, Mumbai, India.
authors.forename: Sinjan
authors.initials: S
authors.lastname: Choudhary
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Kalina Campus, Mumbai, India.
authors.forename: Shreyada N
authors.initials: SN
authors.lastname: Save
authors.affiliation: Department of Chemistry, Indian Institute of Technology-Bombay, Mumbai, India.
authors.forename: Nand
authors.initials: N
authors.lastname: Kishore
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Kalina Campus, Mumbai, India.|Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Ramakrishna V
authors.initials: RV
authors.lastname: Hosur
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D002417:Cattle; D004357:Drug Synergism; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D007328:Insulin / Q000737:chemistry*; D009113:Muramidase / Q000737:chemistry*; D011392:Proline / Q000494:pharmacology*; D066329:Protein Aggregates; D013012:Sorbitol / Q000494:pharmacology*
chemical_list: D007328:Insulin; D066329:Protein Aggregates; D013012:Sorbitol; D011392:Proline; D009113:Muramidase