کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10162375 1114328 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Thiol-Disulfide Exchange in Peptides Derived from Human Growth Hormone
ترجمه فارسی عنوان
تبادل تیویل دی سولفید در پپتیدهای حاصل از هورمون رشد انسانی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی
Disulfide bonds stabilize proteins by cross‐linking distant regions into a compact three‐dimensional structure. They can also participate in hydrolytic and oxidative pathways to form nonnative disulfide bonds and other reactive species. Such covalent modifications can contribute to protein aggregation. Here, we present experimental data for the mechanism of thiol-disulfide exchange in tryptic peptides derived from human growth hormone in aqueous solution. Reaction kinetics was monitored to investigate the effect of pH (6.0-10.0), temperature (4-50°C), oxidation suppressants [ethylenediaminetetraacetic acid (EDTA) and N2 sparging], and peptide secondary structure (amide cyclized vs. open form). The concentrations of free thiol containing peptides, scrambled disulfides, and native disulfide‐linked peptides generated via thiol-disulfide exchange and oxidation reactions were determined using reverse‐phase HPLC and liquid chromatography-mass spectrometry. Concentration versus time data were fitted to a mathematical model using nonlinear least squares regression analysis. At all pH values, the model was able to fit the data with R2 ≥ 0.95. Excluding oxidation suppressants (EDTA and N2 sparging) resulted in an increase in the formation of scrambled disulfides via oxidative pathways but did not influence the intrinsic rate of thiol-disulfide exchange. In addition, peptide secondary structure was found to influence the rate of thiol-disulfide exchange. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1032-1042, 2014
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 4, April 2014, Pages 1032-1042
نویسندگان
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