Ultralente insulin has been one of the commercially most important insulin preparations in diabetes treatment over the last 50 years. It is a suspension of insulin microcrystals which dissolve slowly following subcutaneous injection. Because of the small crystal size of about 25 x 25 x 5 microm(3) the atomic structure has been elusive until now. Here we present the crystal structures from Ultralente and their precursor microcrystals from the industrial manufacturing process. During this process insulin undergoes a conformational change within the microcrystals. Both structures show canonical folding of the insulin molecules but exhibit a number of new features when compared with other insulin structures. Surprisingly, we found that the Ultralente crystals bind the conservation agent methylparaben, which slows down dissolution of the crystals and thus contributes to the long duration of action.

译文

在过去的50年中,Ultralente胰岛素一直是糖尿病治疗中商业上最重要的胰岛素制剂之一。它是胰岛素微晶的悬浮液,在皮下注射后会缓慢溶解。由于晶体尺寸约为25x5 microm(3),因此原子结构一直难以捉摸。在这里,我们介绍了Ultralente的晶体结构及其工业制造过程中的前体微晶。在此过程中,胰岛素在微晶内发生构象变化。两种结构均显示出胰岛素分子的典型折叠,但与其他胰岛素结构相比,表现出许多新功能。令人惊讶的是,我们发现超烯晶体与守恒剂对羟基苯甲酸甲酯结合,从而减慢了晶体的溶解,从而有助于作用的持续时间长。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录