Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstr. 22, 64287 Darmstadt, Germany.
Chembiochem. 2013 Jan 2;14(1):137-46. doi: 10.1002/cbic.201200604. Epub 2012 Dec 11.
Bioactive peptides often contain several disulfide bonds that provide the main contribution to conformational rigidity and structural, thermal, or biological stability. Among them, cystine-knot peptides-commonly named "knottins"-make up a subclass with several thousand natural members. Hence, they are considered promising frameworks for peptide-based pharmaceuticals. Although cystine-knot peptides are available through chemical and recombinant synthetic routes, oxidative folding to afford the bioactive isomers still remains a crucial step. We therefore investigated the oxidative folding of ten protease-inhibiting peptides from two knottin families, as well as that of an HIV entry inhibitor and of aprotinin, under two conventional sets of folding conditions and by a newly developed procedure. Kinetic studies identified folding conditions that resulted in correctly folded miniproteins with high rates of conversion even for highly hydrophobic and aggregation-prone peptides in concentrated solutions.
生物活性肽通常含有几个二硫键，这些二硫键对构象刚性和结构、热或生物稳定性有主要贡献。其中，半胱氨酸结肽通常被称为“结肽”，构成了具有几千个天然成员的一个亚类。因此，它们被认为是基于肽的药物的有前途的框架。尽管半胱氨酸结肽可通过化学和重组合成途径获得，但氧化折叠以获得生物活性异构体仍然是一个关键步骤。因此，我们研究了来自两个结肽家族的十种蛋白酶抑制剂肽、一种 HIV 进入抑制剂和抑肽酶的氧化折叠，分别在两种常规折叠条件下和一种新开发的方法下进行。动力学研究确定了折叠条件，即使在高浓度溶液中，对于高度疏水和易于聚集的肽，也能以高转化率得到正确折叠的小蛋白。
