Gori Alessandro, Gagni Paola, Rinaldi Silvia
Istituto di Chimica del Riconoscimento Molecolare (ICRM), National Research Council of, Italy) (CNR, via Mario Bianco 9, 20131, Milano, Italy.
Chemistry. 2017 Oct 26;23(60):14987-14995. doi: 10.1002/chem.201703199. Epub 2017 Aug 23.
The activity profile of many biologically relevant proteins and peptides often relies on a precise 3D structural organization. In this context, disulfide bonds are natural covalent constraints that play a key role in driving and stabilizing the folding pattern of these molecules. Despite its prominent significance as structural motif, the disulfide bond itself is inherently unstable under physiological conditions, posing a major limit to the use and development of disulfide-rich peptides and proteins as molecular tools and drug lead compounds. To tackle this restriction, disulfide engineering with stable functional analogues has arisen a considerable interest. Here, the most popular approaches to disulfide replacement are reviewed and discussed with particular emphasis on advantages and limitations under both functional and synthetic perspectives.
许多具有生物学相关性的蛋白质和肽的活性特征通常依赖于精确的三维结构组织。在这种情况下，二硫键是天然的共价限制因素，在驱动和稳定这些分子的折叠模式中起关键作用。尽管二硫键作为结构基序具有显著意义，但在生理条件下其本身固有地不稳定，这对富含二硫键的肽和蛋白质作为分子工具和药物先导化合物的使用和开发构成了主要限制。为了解决这一限制，用稳定的功能类似物进行二硫键工程已引起了相当大的兴趣。在此，将对最流行的二硫键替代方法进行综述和讨论，特别强调在功能和合成两个方面的优点和局限性。
