Chemical synthesis and racemic crystallization of rat C5a-desArg
Chemical synthesis and racemic crystallization of rat C5a-desArg
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大鼠C5a-desArg的化学合成及外消旋结晶
DOI：
10.1016/j.cclet.2019.08.039
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发表时间：
2020-03
期刊：
影响因子：
--
通讯作者：
Ge-Min Fang
中科院分区：
文献类型：
--
作者：
Chao Zuo;Baochang Zhang;Meng Wu;Donald Bierer;Jing Shi;Ge-Min Fang
过敏毒素蛋白 C5a C 端精氨酸的缺失会降低其受体结合亲和力。了解 C 末端精氨酸如何影响 C5a 的结构和生物活性对于开发 C5a C 末端模拟物作为候选药物非常重要。在此，我们报道了大鼠C5a及其C端精氨酸缺失的d-对映体的全化学合成，即l-rC5a-desArg和d-rC5a-desArg。随后首次通过外消旋晶体学确定了rC5a-desArg的结构。发现rC5a-Arg的C端残基从第四螺旋开始以连续的螺旋构象扩展。该C端构象与之前报道的全长C5a的C端构象显着不同，表明C端精氨酸残基的删除可能导致C5a中两个相邻Arg残基形成的带正电表面的破坏。
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 itsd-enantiomer with its C-terminal arginine deleted, namelyl-rC5a-desArg andd-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 conformation. 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.
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影响因子：
15
作者：
Pentelute BL;Gates ZP;Tereshko V;Dashnau JL;Vanderkooi JM;Kossiakoff AA;Kent SB
通讯作者：
Kent SB
影响因子：
3.7
作者：
Nandakumar KS;Jansson A;Xu B;Rydell N;Ahooghalandari P;Hellman L;Blom AM;Holmdahl R
通讯作者：
Holmdahl R
影响因子：
--
作者：
Shan Tang;Yanyan Si;Zhi-Peng Wang;Kunrong Mei;Xin Chen;Jing Cheng;Ji‐Shen Zheng;Lei Liu
通讯作者：
Shan Tang;Yanyan Si;Zhi-Peng Wang;Kunrong Mei;Xin Chen;Jing Cheng;Ji‐Shen Zheng;Lei Liu
影响因子：
--
作者：
Ho-Lun Yeung;C. Squire;Y. Yosaatmadja;S. Panjikar;G. López;A. Molina;E. Baker;P. Harris;M. Brim
通讯作者：
Ho-Lun Yeung;C. Squire;Y. Yosaatmadja;S. Panjikar;G. López;A. Molina;E. Baker;P. Harris;M. Brim
C5a 受体拮抗剂的正构和变构作用
影响因子：
16.8
作者：
Liu, Heng;Kim, Hee Ryung;Zhang, Cheng
通讯作者：
Zhang, Cheng