Boehm J C, Kingsbury W D, Perry D, Gilvarg C
J Biol Chem. 1983 Dec 25;258(24):14850-5.
We describe a method by which sulfhydryl compounds may be transported into Escherichia coli as the mixed disulfides with a cysteine residue of a di- or tripeptide. Transport occurs through the di- or oligopeptide transport systems, and it is suggested that subsequent release of the sulfhydryl compound occurs as a result of a disulfide exchange reaction with components of the sulfhydryl-rich cytoplasm. The free sulfhydryl compounds used here (2-mercaptopyridine and 4-[N-(2-mercaptoethyl)]aminopyridine-2,6-dicarboxylic acid) show weak growth-inhibitory properties in their own right, but disulfide linkage to a cysteinyl peptide results in a considerable enhancement (up to 2 orders of magnitude). This is the first example of the use of the peptide transport systems of E. coli to effect portage transport of a poorly permeant molecule by using attachment to the side chain of one of the amino acid residues of a peptide; all previous examples have involved the incorporation of amino acid analogues into the peptide backbone. The synthesis of cysteinyl peptides containing disulfide-linked 2-mercaptopyridine is described. Displacement of the 2-mercaptopyridine by sulfhydryl compounds of interest proceeds rapidly and quantitatively in aqueous alkaline solution to provide the required peptide disulfides.
我们描述了一种方法，通过该方法巯基化合物可以作为与二肽或三肽的半胱氨酸残基形成的混合二硫键被转运到大肠杆菌中。转运通过二肽或寡肽转运系统进行，并且有人提出，巯基化合物随后的释放是由于与富含巯基的细胞质成分发生二硫键交换反应的结果。这里使用的游离巯基化合物（2-巯基吡啶和4-[N-(2-巯基乙基)]氨基吡啶-2,6-二羧酸）本身具有较弱的生长抑制特性，但与半胱氨酰肽形成二硫键会导致显著增强（高达2个数量级）。这是首次利用大肠杆菌的肽转运系统，通过与肽的一个氨基酸残基的侧链连接来实现对渗透性差的分子进行携带运输；之前所有的例子都涉及将氨基酸类似物掺入肽主链中。本文描述了含有二硫键连接的2-巯基吡啶的半胱氨酰肽的合成。在碱性水溶液中，目标巯基化合物能快速且定量地取代2-巯基吡啶，从而得到所需的肽二硫键。
