%0 Journal Article
%T STUDIES ON PROLONGED ACTING INSULIN MOLECULAR DESIGN<br>长效胰岛素的分子设计研究
%A Wang Dacheng Zeng Zonghao Ye Yuanjie Lei Kejian Wang Jiahuai
%A <br>王大成
%A 曾宗浩
%A 叶元杰
%A 雷克健
%A 王家槐
%J 生物物理学报
%D 1992
%I 
%X In order to prepare soluble and prolonged-acting insulin derivatives which is mainly directed by intramolecular interactions, a principle is proposed. That is, making some additional non-covalent bonds between monomers of insulin oligomer through residue modification so as to slow down the dissociation rate of insulin hexamer injected into the body and produce the protraction from a depot-effect. On the basis of this idea and the fine structure of insulin, molecular design and computer modelling have been undertaken which provided some rational schemes for site-directed mutagenesis mainly dealing with N-and C-terminal residues of B chain. Among others, B2-Lys/Arg and B31-Lys/Arg substitutions were analysed in some detail and semisynthseized chemically as target samples. Biological tests in rabbits showed that they really both exhibited protracted glucose lowering effects. Furthermore an X-ray structure analysis of B31-Arg human insulin has also been completed at 2 A resolution and showed a pair of additional charged hydrogen bond formed by Arg-B31 and Glu-B21 of the neighbouring monomer in a dimer, that should be the structural basis of such prolonged action. This demonstrates the rationality of our idea for the molecular design.
%K Prolonged-acting insulin
%K Molecular design
%K Computer simulation
%K Derivative B2-Lys/Arg
%K B31-Lys/Arg<br>长效胰岛素
%K 分子设计
%K 计算机模拟
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=E0C9D9BBED813D6674AC13E942EAC86D&aid=BCF0741527DF91D02D3B48AC2C96875C&yid=F53A2717BDB04D52&vid=5D311CA918CA9A03&iid=E158A972A605785F&sid=ED9DF3402785F68D&eid=5568599C60D4BE87&journal_id=1000-6737&journal_name=生物物理学报&referenced_num=0&reference_num=4