Chemical synthesis of ComX pheromone and related peptides containing isoprenoidal tryptophan residues
Chemical synthesis of ComX pheromone and related peptides containing isoprenoidal tryptophan residues
复制标题
DOI：
10.1016/j.tet.2006.06.074
复制
发表时间：
2006-09-18
期刊：
影响因子：
2.1
通讯作者：
Sakagami, Youji
中科院分区：
文献类型：
--
作者：
Okada, Masahiro;Sato, Isao;Sakagami, Youji
ComX信息素是一种翻译后修饰的寡肽，可以刺激枯草芽孢杆菌群体感应控制的自然遗传能力。最近，菌株RO-E-2产生的COMX(RO-E-2)信息素的结构被确定。根据核磁共振分析，香叶基与色氨酸残基结合，形成三环结构。提出了四种可能的立体化学异构体中的一种是基于对模型化合物的构象搜索和假设天然信息素中的氨基酸残基具有L构型。合成了所有可能的修饰色氨酸残基和相应的COmX(RO-E-2)多肽，以证实精确的立体化学。本文详细报道了这些修饰色氨酸衍生物的合成。成功地合成了4种光学活性的修饰色氨酸甲酯，并由此合成了4种非对映异构体COmX(RO-E-2)多肽。由于四个非对映异构体中只有一个在光谱上与天然信息素相同并且具有生物活性，因此能够明确地建立COmX(RO-E-2)信息素的绝对结构。此外，在与COmX(RO-E-2)信息素共纯化的发酵液中还存在另外两种生物活性信息素。通过LC-MS和核磁共振分析，推测这些信息素是COmX(RO-E-2)信息素的N端截短肽，即[2-6]COmX(RO-E-2)和[3-6]COmX(RO-E-2)。利用Fmoc固相法合成了COmX(RO-E-2)信息素和[2-6]COmX(RO-E-2)和[3-6]COmX(RO-E-2)多肽。合成的多肽与天然信息素完全相同，并具有明显的生物活性。(C)2006爱思唯尔有限公司。保留所有权利。
The ComX pheromone is a post-translationally modified oligopeptide that stimulates natural genetic competence controlled by quorum sensing in Bacillus subtilis. Recently, the structure of the ComX(RO-E-2) pheromone produced by strain RO-E-2 was determined. Based on the NMR analysis, a geranyl group is bound to the tryptophan residue, which results in the formation of a tricyclic ring structure. It was proposed that one of the four possible stereochemical isomers was based on a conformational search for model compounds and the assumption that amino acid residues in the natural pheromone have the L-configuration. All possible modified tryptophan residues and the corresponding COmX(RO-E-2) peptides were synthesized to confirm the precise stereochemistry. Here, the synthesis of the modified tryptophan derivatives was reported in detail. It was succeeded in synthesizing four optically active modified tryptophan methyl esters from which the four diastereomeric COmX(RO-E-2) peptides were prepared. Since only one of the four diastereomers was spectroscopically identical to the natural pheromone and exhibited biological activity, the absolute structure of the COmX(RO-E-2) pheromone was able to be established unambiguously. Furthermore, it was noticed that two other bioactive pheromones were present in the culture broth that were co-purified with COmX(RO-E-2) pheromone. These pheromones were presumed to be the N-terminal truncated peptides Of COmX(RO-E-2) pheromone, i.e., [2-6]COmX(RO-E-2) and [3-6]COmX(RO-E-2), by LC-MS and NMR analyses. Using Fmoc solid-phase peptide synthesis, COmX(RO-E-2) pheromone and the [2-6]COmX(RO-E-2) and [3-6]COmX(RO-E-2) peptides were prepared. The synthetic peptides were identical to the natural pheromones and also showed significant biological activity. (c) 2006 Elsevier Ltd. All rights reserved.