肽中的二硫键有助于其结构的固定和刚性,导致生物活性的表达和对代谢酶的抗性。此外,二硫键在包含两个生物活性分子如肽的缀合物的构建中是重要的,糖和药物。因此,二硫键形成的新方法有助于更有效地构建二硫键产物。本文综述了利用3-硝基-2-吡啶磺酸基(Npys)化合物合成二硫键形成方法的研究进展。我们通过使用Npys树脂开发了一种一锅式固相二硫键连接(SPDSL)方法,这可以容易地提供使用两种类型的含硫醇组分(例如肽和小分子)产生的不对称二硫键。可以容易地制备疏水性分子和亲水性肽之间的二硫键连接的缀合。基于SPDSL战略,我们还开发了二硫键驱动的环肽合成,这代表了从两个不同片段制备环肽的新策略。通过在两个片段之间产生二硫键,可以实现有利的分子内酰胺键形成,导致偶联位点外消旋化的减少。我们发现3-硝基-2-吡啶磺酸甲酯(Npys-OMe)充当二硫键形成试剂,具有轻度氧化活性。该试剂增强了两个硫醇之间的分子内二硫键形成,以在弱酸性条件下合成环肽。作为Npys-OMe的应用,我们证明了在含硫醇的肽基树脂上二硫键的形成。
Disulfide bonds in peptides contribute to the immobilization and rigidity of their structures, leading to the expression of biological activity and resistance to metabolic enzymes. In addition, disulfide bonds are important in the construction of conjugates comprising two bioactive molecules such as peptides, sugars and drugs. Therefore, new methods of disulfide bond formation contribute to a more efficient construction of disulfide products. This article reviews studies on development of synthetic methodology for disulfide bond formation by using 3-nitro-2-pyridinesulfenyl (Npys) compounds. We have developed a one-pot solid-phase disulfide ligation (SPDSL) method by using an Npys resin, which can easily afford an asymmetric disulfide bond that is generated using two types of thiol-containing components such as peptides and small molecules. The disulfide-linked conjugation between a hydrophobic molecule and a hydrophilic peptide can be easily prepared. Based on the SPDSL strategy, we also developed a disulfide-driven cyclic peptide synthesis, which represents a new strategy to prepare cyclic peptides from two different fragments. By generating a disulfide bond between two fragments, the entropically favorable intramolecular amide bond formation can be achieved, resulting in the reduction of racemization at the coupling site. We found that methyl 3-nitro-2-pyridinesulfenate (Npys-OMe) functions as a disulfide bond-forming reagent possessing mildly oxidative activity. This reagent enhances intramolecular disulfide bond formation between two thiols for the synthesis of cyclic peptides under mildly acidic conditions. As the applications of Npys-OMe, we demonstrated the disulfide bond formation on thiols-containing peptidyl resin.