5UDP

High resolution x-ray crystal structure of synthetic insulin lispro

5UDP の概要

• エントリーDOI: 10.2210/pdb5udp/pdb
• 分子名称: Insulin Lispro A chain, Insulin Lispro B chain, PHENOL, ... (7 entities in total)
• 機能のキーワード: insulin lispro, chemical protein synthesis, fmoc chemistry, hormone
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P01308 P01308
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 35695.29

構造登録者

Mandal, K.,Dhayalan, B.,Kent, S.B.H. (登録日: 2016-12-28, 公開日: 2017-01-11, 最終更新日: 2024-11-20)

主引用文献

Dhayalan, B.,Mandal, K.,Rege, N.,Weiss, M.A.,Eitel, S.H.,Meier, T.,Schoenleber, R.O.,Kent, S.B.
Scope and Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin.
Chemistry, 23:1709-1716, 2017

PubMed Abstract: We have systematically explored three approaches based on 9-fluorenylmethoxycarbonyl (Fmoc) chemistry solid phase peptide synthesis (SPPS) for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the "hybrid method", in which maximally protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide-thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[O-β-(Thr)] ester-linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS. The most effective method for the preparation of the 51 residue ester-linked polypeptide chain of ester insulin was the use of unprotected peptide-thioester segments, prepared from peptide-hydrazides synthesized by Fmoc chemistry SPPS, and condensed by native chemical ligation. High-resolution X-ray crystallography confirmed the disulfide pairings and three-dimensional structure of synthetic insulin lispro prepared from ester insulin lispro by this route. Further optimization of these pilot studies could yield an efficient total chemical synthesis of insulin lispro (Humalog) based on peptide synthesis by Fmoc chemistry SPPS.

PubMed: 27905149
DOI: 10.1002/chem.201605578

実験手法

X-RAY DIFFRACTION (1.348 Å)