Chemical synthesis and racemic crystallization of rat C5a-desArg  

作　　者：Chao Zuo Baochang Zhang Meng Wu Donald Bierer Jing Shi Ge-Min Fang 

机构地区：[1]School of Life Science,Institutes of Physical Science and InformationTechnology,Anhui University,Hefei 230601,China [2]Department of Chemistry,Tsinghua University,Beijing 100084,China [3]Department of Chemistry,University of Science and Technology of China,Hefei 230601,China [4]Bayer AG,Department of Medicinal Chemistry,Aprather Weg 18A,42096,Wuppertal,Germany

出　　处：《Chinese Chemical Letters》2020年第3期693-696,共4页中国化学快报（英文版）

基　　金：supported by the National Key R&D Program of China(No.2017YFA0505200);the National Natural Science Foundation of China(Nos.21532004,21807001,91753205,81621002,21621003)。

摘　　要：The deletion of the C-terminal arginine of the anaphylatoxin protein C5a reduces it receptor binding affinity.Understanding how C-terminal arginine affects the structure and bioactivity of C5a is important for the development of C5a C-terminal mimics as drug candidates.Herein,we report the total chemical synthesis of rat C5a and its D-enantiomer with its C-terminal arginine deleted,namely L-rC5a-desArg and D-rC5a-desArg.The structure of rC5a-desArg was then determined by racemic crystallography for the first time.The C-terminal residues of rC5a-Arg were found to expand from the fourth helix in a continuous helical confo rmation.This C-terminal conformation is significantly different from that of the previously reported full-length of C5a,indicating that the deletion of C-terminal arginine residue could result in the destruction of a positively charged surface formed by two adjacent Arg residues in C5a.

关 键 词：ANAPHYLATOXIN C5a RACEMIC CRYSTALLIZATION Solid phase peptide SYNTHESIS CHEMICAL protein SYNTHESIS Hydrazide-based native CHEMICAL ligation 

分 类 号：TQ464[化学工程—制药化工]