Total chemical synthesis of a biologically active and homogeneous analog of Human Growth Hormone [Nle14,125,170,Glu29,91,Gln74, Asn107,Asp109]hGH-NH2 by sequential native chemical ligation

TETRAHEDRON LETTERS

卷:58

Article

Sueiras-Diaz, Javier¹  Zhang, Ying¹  Velentza, Anastasia¹  Santoso, Buyung¹  Yang, Suijin¹ 

[1] Ferring Res Inst, 4245 Sorrento Valley Blvd, San Diego, CA 92121 USA

关键词: Human Growth Hormone analog;    Microwave-assisted SPPS;    Native chemical ligation;    N-Acyl-N '-methylacylurea linker;    Selective desulfurization;   

DOI  :  10.1016/j.tetlet.2017.05.027

来源: Elsevier

【 摘 要 】

We report herein, for the first time, a sequential total chemical synthesis of the Human Growth Hormone analog [Nle(14,125,170),Giu(29,91),Gln(74), Asn(107),Asp(109)]hGH-NH2, composed of a 191 amino acid residue polypeptide chain containing two disulfide bonds and nine modifications in the natural sequence. Sequential native chemical ligation of three discrete segments of 52, 52 and 87 amino acid residues gave the target full-length polypeptide chain. Subsequent folding with concomitant formation of the native disulfide bonds afforded a correctly folded homogeneous analog which is biologically active. (C) 2017 The Authors. Published by Elsevier Ltd.

【 授权许可】

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