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Facile synthesis of macrocyclic peptide toxins of GpTx-1 and its analogue†
Organic Chemistry Frontiers ( IF 4.6 ) Pub Date : 2018-06-02 00:00:00 , DOI: 10.1039/c8qo00415c Chao Chen 1, 2, 3, 4, 5 , Mei Hong 1, 2, 3, 4, 5 , Xiaoqi Guo 5, 6, 7, 8, 9 , Fangming Wu 5, 9, 10, 11 , Changlin Tian 5, 6, 7, 8, 9 , Yangding Wang 1, 2, 3, 4, 5 , Zhaoqing Xu 12, 13, 14, 15, 16
Organic Chemistry Frontiers ( IF 4.6 ) Pub Date : 2018-06-02 00:00:00 , DOI: 10.1039/c8qo00415c Chao Chen 1, 2, 3, 4, 5 , Mei Hong 1, 2, 3, 4, 5 , Xiaoqi Guo 5, 6, 7, 8, 9 , Fangming Wu 5, 9, 10, 11 , Changlin Tian 5, 6, 7, 8, 9 , Yangding Wang 1, 2, 3, 4, 5 , Zhaoqing Xu 12, 13, 14, 15, 16
Affiliation
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GpTx-1, a 34-residue peptide cross-linked by three disulfide bridges, originally isolated from the venom of the tarantula Grammostola porter, and its analogue GpTx-1-71 ([Ala5,Phe6,Leu26,Arg28]GpTx-1) are highly potent pharmaceutical inhibitor candidates to voltage-gated sodium channels, currently in preclinical development. GpTx-1 and its analogue for drug development had previously been obtained by adopting a tedious stepwise solid phase peptide synthesis strategy. Herein, we present a flexible and highly practical strategy by converging three segments based on C-terminal proline residues. This approach provided a reliable and convenient synthetic route which could greatly facilitate GpTx-1 based drug developments for pain relief. Solution NMR structural analysis and electrophysiology evaluation verified the compositional and functional characteristics of the two macrocyclic peptides, which are consistent with previous studies.
中文翻译：
轻松合成GpTx-1及其类似物的大环肽毒素†
GpTx-1，34个残基的肽，由三个二硫键交联，最初是从狼蛛的革兰氏菌搬运工的毒液中分离出来的，及其类似物GpTx-1-71（[Ala5，Phe6，Leu26，Arg28] GpTx-1）是电压门控钠通道的高效药物抑制剂，目前正处于临床前开发阶段。以前已经通过采用乏味的逐步固相肽合成策略获得了用于药物开发的GpTx-1及其类似物。在这里，我们通过基于C末端脯氨酸残基的三个部分汇聚，提出了一种灵活而高度实用的策略。这种方法提供了可靠且方便的合成途径，可以极大地促进基于GpTx-1的药物开发以减轻疼痛。溶液NMR结构分析和电生理评估证实了这两种大环肽的组成和功能特征，与先前的研究一致。
更新日期：2018-06-02
中文翻译：
轻松合成GpTx-1及其类似物的大环肽毒素†
GpTx-1，34个残基的肽，由三个二硫键交联，最初是从狼蛛的革兰氏菌搬运工的毒液中分离出来的，及其类似物GpTx-1-71（[Ala5，Phe6，Leu26，Arg28] GpTx-1）是电压门控钠通道的高效药物抑制剂，目前正处于临床前开发阶段。以前已经通过采用乏味的逐步固相肽合成策略获得了用于药物开发的GpTx-1及其类似物。在这里，我们通过基于C末端脯氨酸残基的三个部分汇聚，提出了一种灵活而高度实用的策略。这种方法提供了可靠且方便的合成途径，可以极大地促进基于GpTx-1的药物开发以减轻疼痛。溶液NMR结构分析和电生理评估证实了这两种大环肽的组成和功能特征，与先前的研究一致。
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