The new era of biotech insulin analogues
The new era of biotech insulin analogues
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DOI：
10.1007/s001250051400
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发表时间：
1997-07-01
期刊：
影响因子：
8.2
通讯作者：
Brange, J
中科院分区：
文献类型：
--
作者：
Brange, J
胰岛素的许多结构特性响应于胰腺β细胞中的生物合成、加工、运输和储存的要求而进化，这些特性对于激素的生物学作用不是必需的。因此，野生型胰岛素对于替代疗法具有远不是最佳的特性并不奇怪。例如，天然人胰岛素与六聚体单元自缔合，这限制了通过各种途径吸收分子的可能性。在过去的十年中，分子设计的新技术已经出现，重组DNA技术为合理的蛋白质药物设计提供了新的和令人兴奋的机会。这篇综述介绍了胰岛素工程的最新进展，旨在优化激素治疗的例子。这些方法集中于改善药代动力学性质、储存稳定性和侵入性较小的给药途径的可行性。
Many of the structural properties of insulin have evolved in response to the requirements of biosynthesis, processing, transport and storage in the pancreatic beta cells, properties that are not necessary for the biological action of the hormone. It is therefore not surprising that wild-type insulin has far from optimal characteristics for replacement therapy. For example, native human insulin self-associates to hexameric units, which limits the possibilities for the absorption of the molecule by various routes. During the last decade new techniques of molecular design have emerged and recombinant DNA technology offers new and exciting opportunities for rational protein drug design. This review describes examples of recent advances in insulin engineering aimed at optimizing the hormone for therapy. Such approaches focus on improvements in the pharmacokinetic properties, storage stability, and feasibility for less intrusive routes of administration.