کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485638 | 1114362 | 2012 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Local Dynamics and Their Alteration by Excipients Modulate the Global Conformational Stability of an lgG1 Monoclonal Antibody
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A molecular understanding of excipient effects on the interrelationship(s) between dynamics and conformational stability of proteins, such as monoclonal antibodies (mAbs), can be important for their pharmaceutical development. The current study examines stabilizing and destabilizing effects of excipients on the conformational stability and local dynamics of distinct solventâexposed regions within an IgG1 monoclonal antibody (mAbâB). The principles of siteâselective photoselection upon redâedge excitation, accompanied by acrylamide quenching of tryptophan fluorescence were employed in this study. The initiation of mAbâB thermal unfolding occurs by structural alterations in the more solventâexposed regions of the antibody, which subsequently leads to a cascade of structural alterations in its relatively more solventâshielded regions. In addition, an increase in internal dynamics of solventâshielded regions made mAbâB more susceptible to thermally induced structural perturbations resulting in its global destabilization. Sucrose and arginine exert their stabilizing and destabilizing effects by predominantly influencing the conformational stability of solventâexposed regions in mAbâB. The complex molecular effects of sucrose and arginine on local dynamics of different regions in mAbâB and their correlation with the protein's conformational stability are described within the pretransition range, at the onset temperature (Tonset) and at the thermal melting temperature (TM).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 12, December 2012, Pages 4444-4457
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 12, December 2012, Pages 4444-4457
نویسندگان
Santosh V. Thakkar, Jae Hyun Kim, Hardeep S. Samra, Hasige A. Sathish, Steven M. Bishop, Sangeeta B. Joshi, David B. Volkin, C. Russell Middaugh,