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JCR 2016
جستجوی مقالات
دوشنبه 24 شهریور 1404
Iranian Journal of Basic Medical Sciences
، جلد ۲۶، شماره ۶، صفحات ۶۳۵-۶۴۴
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عنوان انگلیسی
Amino acid-mPEGs: Promising excipients to stabilize human growth hormone against aggregation
چکیده انگلیسی مقاله
Objective(s): Today, the non-covalent PEGylation methods of protein pharmaceuticals attract more attention and possess several advantages over the covalent approach. In the present study, Amino Acid-mPEGs (aa-mPEGs) were synthesized, and the human Growth Hormone (hGH) stability profile was assessed in their presence and absence.Materials and Methods: aa-mPEGs were synthesized with different amino acids (Trp, Glu, Arg, Cys, and Leu) and molecular weights of polymers (2 and 5 KDa). The aa-mPEGs were analyzed with different methods. The physical and structural stabilities of hGH were analyzed by SEC and CD spectroscopy methods. Physical stability was assayed at different temperatures within certain intervals. Molecular dynamics (MD) simulation was used to realize the possible mode of interaction between protein and aa-mPEGs. The cell-based method was used to evaluate the cytotoxicity.Results: HNMR and FTIR spectroscopy indicated that aa-mPEGs were successfully synthesized. hGH as a control group is known to be stable at 4 °C; a pronounced change in monomer degradation is observed when stored at 25 °C and 37 °C. hGH:Glu-mPEG 2 kDa with a molar ratio of 1:1 to the protein solution can significantly increase the physical stability. The CD spectroscopy method showed that the secondary structure of the protein was preserved during storage. aa-mPEGs did not show any cytotoxicity activities. The results of MD simulations were in line with experimental results.Conclusion: This paper showed that aa-mPEGs are potent excipients in decreasing the aggregation of hGH. Glu-mPEG exhibited the best-stabilizing properties in a harsh environment among other aa-mPEGs.
کلیدواژههای انگلیسی مقاله
Human Growth Hormone, Non-covalent PEGylation, Physical PEGylation, Protein formulation, Stability
نویسندگان مقاله
| Somayeh Vakili
Department of Medical Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| JamshidKhan Chamani
Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| Zeinab Amiri-Tehranizadeh
Department of Medical Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| Hossein Hosseinzadeh
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran|Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| Fatemeh Mosaffa
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| Seyed-Mola Khatami
Department of Chemistry, Faculty of Samen Hojaj, Mashhad Branch, Technical and Vocational University (TVU), Tehran, Iran
| Bahman Khameneh Bagheri
Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| Mohammad Reza Saberi
Department of Medical Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
نشانی اینترنتی
https://ijbms.mums.ac.ir/article_22134.html
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