A morphological screening of protein crystals for interferon delivery by metal ion-chelate technology
A morphological screening of protein crystals for interferon delivery by metal ion-chelate technology
复制标题
通过金属离子螯合技术对用于干扰素递送的蛋白质晶体进行形态学筛选
DOI：
10.3109/03639045.2010.481303
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发表时间：
2010-11
影响因子：
3.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Shi K;Jiang Y;Cui F;Wang S;Li X
目标：方法：以重组人干扰素α-2b（rhIFN α-2b）为模型蛋白质药物，采用悬滴气相扩散法进行结晶。结果：考察了晶种蛋白浓度、悬滴pH值、平衡液离子强度、沉淀剂等关键因素对晶体形成的影响。分子排阻色谱、抗病毒活性测定和酶联免疫吸附试验表明，结晶过程对rhIFN的分子完整性和生物学效价均无明显影响。此外，在体外释放行为的rhIFN从晶格的特点是由一个初始的快速释放，然后由一个持续释放长达48 hour.Conclusion：这里所描述的工作提出了一个令人兴奋的可能性，治疗性蛋白质晶体作为一种长效制剂。
Objective: This study presents a preliminary exploration on extending the half-life of therapeutic proteins by crystallization strategy without new molecular entities generation.Methods: Recombinant human interferon (rhIFN) α-2b, a model protein drug in this case, was crystallized using a hanging-drop vapor diffusion method. A novel chelating technique with metal ions was employed to promote crystals formation.Results: The effects of key factors such as seeding protein concentration, pH of the hanging drop, ionic strength of the equilibration solution, and precipitants were investigated. Size-exclusion liquid chromatography, antiviral activity determination, and enzyme-linked immunosorbent assay indicated that both the molecular integrity and biological potency of rhIFN were not significantly affected by crystallization process. In addition, the in vitro release behavior of rhIFN from crystal lattice was characterized by an initial fast release, followed by a sustained release up to 48 hour.Conclusion: The work described here suggested an exciting possibility of therapeutic protein crystals as a long-acting formulation.
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DOI：
--
发表时间：
2001
期刊：
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
影响因子：
--
作者：
M. Grace;S. Youngster;G. Gitlin;W. Sydor;L. Xie;L. Westreich;S. Jacobs;D. Brassard;J. Bausch;R. Bordens
通讯作者：
M. Grace;S. Youngster;G. Gitlin;W. Sydor;L. Xie;L. Westreich;S. Jacobs;D. Brassard;J. Bausch;R. Bordens
影响因子：
5.7
作者：
Radhakrishnan, R;Walter, LJ;Walter, MR
通讯作者：
Walter, MR
影响因子：
46.9
作者：
Brader, ML;Sukumar, M;Myers, SR
通讯作者：
Myers, SR
影响因子：
3.1
作者：
I. Degim;N. Çelebi
通讯作者：
I. Degim;N. Çelebi
影响因子：
6.7
作者：
Glue, P;Fang, JWS;Jacobs, S
通讯作者：
Jacobs, S