کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487325 | 1114412 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Dimerization of a PACAP peptide analogue in DMSO via asparagine and aspartic acid residues
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کلمات کلیدی
HPLC (high‐performance/pressure liquid chromatography)Deamidation - انحلالPeptide delivery - تحویل پپتیدStability - ثباتPhysical stability - ثبات فیزیکیPhysical characterization - خصوصیات فیزیکیDehydration - دهیدراسیون، کمآبی بدنMass spectrometry - طیف سنجی جرمیFormulation - فرمولاسیونPeptides - پپتیدها
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
To optimize the stability of a peptide development candidate for the treatment of type II diabetes, formulation studies were initiated in organic solvents and compared to results obtained in aqueous solutions. Stability was assessed by reversed phase liquid chromatography (RPLC) and electrospray ionization mass spectrometry (ESIâMS). Previous studies had shown deamidation and hydrolysis to be the primary mechanisms of degradation in aqueous formulations. Surprisingly, the use of an organic solvent did not decrease the rate of degradation and, as presented here, produced degradation products including dimers. We propose here that deamidation can readily occur in polar anhydrous organic solvents such as DMSO and that the dimer forms through intermolecular nucleophilic attack of an amino acid side chain on a stabilized cyclic imide intermediate. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 97:1246-1256, 2008
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 3, March 2008, Pages 1246-1256
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 3, March 2008, Pages 1246-1256
نویسندگان
Joanne C. Severs, Wayne A. Froland,