title: New insights into side effect of solvents on the aggregation of human islet amyloid polypeptide 11-20.
abstract: The formation of highly ordered fibrils for the human islet amyloid polypeptide (hIAPP) is considered as one of the precipitating factors of type 2 diabetes mellitus. In this study, an emerging new approach microscale thermophoresis and conventional ThT fluorescence assay were utilized to investigate the aggregation behavior of hIAPP(11-20), giving a new insight of the solvent effect on the aggregation of hIAPP(11-20). hIAPP(11-20) displayed different aggregation behaviors in various buffers, revealing that hIAPP(11-20) not only self-aggregates but also binds to solvent components. hIAPP(11-20) had a higher binding affinity for Tris than other selected buffers because multiple hydrogen bonds form, resulting in weaker self-aggregation of hIAPP(11-20) at the early stage of aggregation and prolonging the fibril formation process. hIAPP(11-20) displayed similar self-aggregation in both HEPES and pure water. Negatively charged phosphate ions in the PBS solution 'neutralize' the charges carried by hIAPP(11-20) itself to some extent, causing rapid aggregation of hIAPP(11-20), and leading to a shorter fibrillation process of hIAPP(11-20). These results revealed that solvents contribute to the aggregation of hIAPP(11-20) and demonstrated the affect of solvents on the activity of biomolecules. Additionally, as a new technique, microscale thermophoresis offers a powerful and promising approach to study the early stages of aggregation of peptides or proteins.
authors.affiliation: College of Chemistry and Molecular engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Yexuan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: College of Chemistry and Molecular engineering, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: yulanlan@zzu.edu.cn.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Yu
authors.affiliation: College of Chemistry and Molecular engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Yang
authors.affiliation: National Engineering Laboratory for Wheat & Corn Further Processing, Henan University of Technology, Zhengzhou 450001, PR China.
authors.forename: Chuanguo
authors.initials: C
authors.lastname: Ma
authors.affiliation: College of Chemistry and Molecular engineering, Zhengzhou University, Zhengzhou 450001, PR China; Department of Environmental Engineering and Chemistry, Luoyang Institute of Science and Technology, Luoyang 471023, PR China.
authors.forename: Ling-bo
authors.initials: LB
authors.lastname: Qu
authors.affiliation: Center for Intelligent Chemical Instrumentation, Department of Chemistry and Biochemistry, Clippinger Laboratories, OHIO University, Athens, OH 45701-2979 USA.
authors.forename: Peter de B
authors.initials: Pde B
authors.lastname: Harrington
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D066329:Protein Aggregates / Q000187:drug effects / Q000502:physiology*; D012997:Solvents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D058228:Islet Amyloid Polypeptide; D066329:Protein Aggregates; D012997:Solvents
keywords: Amyloid formation; Islet amyloid polypeptide; Microscale thermophoresis; Molecular interaction; Solvent effect