An Efficient One-Pot Four-Segment Condensation Method for Protein Chemical Synthesis

• Published in: Angewandte Chemie International Edition Vol. 54; no. 19; pp. 5713 - 5717
• Main Authors: Tang, Shan, Si, Yan-Yan, Wang, Zhi-Peng, Mei, Kun-Rong, Chen, Xin, Cheng, Jing-Yuan, Zheng, Ji-Shen, Liu, Lei
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.05.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Activated; Adjustment; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Chemokine CCL21 - chemical synthesis; Chemokine CCL21 - chemistry; Condensation; Condensing; Cysteine; Human; Humans; native chemical ligation; Peptides; Peptides - chemistry; Physical Sciences; Plant Proteins - chemical synthesis; Plant Proteins - chemistry; protecting groups; protein chemical synthesis; Proteins; Science & Technology; Segments; solid-phase synthesis; Synthesis; SITE; HYDRAZIDES; CCL21; PEPTIDE LIGATION-DESULFURIZATION; X-RAY-STRUCTURE; peptides; protein chemical synthesis; CRAMBIN; solid-phase synthesis; N-SULFANYLETHYLANILIDE PEPTIDE; STRATEGIES; protecting groups; CHEMOKINE; native chemical ligation
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201500051

Successive peptide ligation using a one‐pot method can improve the efficiency of protein chemical synthesis. Although one‐pot three‐segment ligation has enjoyed widespread application, a robust method for one‐pot four‐segment ligation had to date remained undeveloped. Herein we report a new one‐pot multisegment peptide ligation method that can be used to condense up to four segments with operational simplicity and high efficiency. Its practicality is demonstrated by the one‐pot four‐segment synthesis of a plant protein, crambin, and a human chemokine, hCCL21. Pick up a peptide: Tfacm‐protected cysteine is readily activated by pH adjustment, enabling the development of a highly efficient one‐pot four‐segment ligation method. Two proteins, crambin and the chemokine hCCL21, are prepared using this rapid and high‐yielding synthetic route.