کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8994344 | 1114390 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effects of acidic Nâ+â1 residues on asparagine deamidation rates in solution and in the solid state
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Effects of acidic Nâ+â1 residues on asparagine deamidation rates in solution and in the solid state Effects of acidic Nâ+â1 residues on asparagine deamidation rates in solution and in the solid state](/preview/png/8994344.png)
چکیده انگلیسی
The deamidation kinetics of four model peptides (AcGQNGG, AcGQNDG, AcGQNEG, and AcGQNQG) were studied in solution (70°C, pH 5-10) and in lyophilized solids [70°C, 50% relative humidity, “effective pH” ('pH') 5-10] containing polyvinyl pyrrolidone. AcGQNGG, AcGQNEG, and AcGQNQG degraded exclusively through Asn deamidation, whereas AcGQNDG also displayed Asp isomerization, and AspâGly peptide bond cleavage. The pH/'pH'ârate profiles were consistent with a shift in the rateâdetermining step of Asn deamidation from carbonyl addition to expulsion of ammonia with increasing pH. In solution, AcGQNGG deamidated up to 38âfold faster than the other peptides, indicating the importance of steric effects of the Nâ+â1 residue. AcGQNGG and AcGQNQG had up to 60 times slower rates of deamidation in the solid state than in solution. In contrast, the deamidation rates of AcGQNEG and AcGQNDG in the solid state were similar to those in solution. Nâ+â1 Glu or Asp residue may enhance local hydration, so that the deamidation of Asn in the solid formulations actually proceeds in a solutionâlike environment. © 2005 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 94:666-675, 2005
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 94, Issue 3, March 2005, Pages 666-675
Journal: Journal of Pharmaceutical Sciences - Volume 94, Issue 3, March 2005, Pages 666-675
نویسندگان
B.e.i. Li, Eric M. Gorman, Kimberly D. Moore, Todd Williams, Richard L. Schowen, Elizabeth M. Topp, Ronald T. Borchardt,