Hosseini Azade S, Wang Wenjian, Haeffner Fredrik, Gao Jianmin
Department of Chemistry, Boston College, Chestnut Hill, MA, 02467, USA.
Chembiochem. 2017 Mar 2;18(5):479-482. doi: 10.1002/cbic.201600667. Epub 2017 Feb 2.
Cyclic peptides have been proposed as privileged scaffolds that might mimic the folding and function of natural proteins. However, simple cyclic peptides typically cannot fold into well-defined structures. Herein, we describe a foldable cyclic peptide scaffold on which functional side chains can be displayed for targeted recognition of biomolecules. The foldable scaffold is based on prolinomycin, a proline-rich analogue of valinomycin. We report synthetic mutants of prolinomycin that retain the metal-assisted folding behavior under physiological conditions. The predictable structure formation of prolinomycin makes it a powerful platform to enable the development of synthetic receptors for biomolecules of interest. We demonstrate the potential of this scaffold by creating prolinomycin mutants that selectively bind anionic vesicles and bacterial cells.
环肽被认为是一种可能模拟天然蛋白质折叠和功能的优势骨架。然而，简单的环肽通常无法折叠成明确的结构。在此，我们描述了一种可折叠的环肽骨架，在其上可以展示功能性侧链以实现对生物分子的靶向识别。这种可折叠骨架基于脯氨霉素，它是缬氨霉素的富含脯氨酸的类似物。我们报道了脯氨霉素的合成突变体，其在生理条件下保留了金属辅助折叠行为。脯氨霉素可预测的结构形成使其成为开发用于感兴趣生物分子的合成受体的强大平台。我们通过创建选择性结合阴离子囊泡和细菌细胞的脯氨霉素突变体来证明这种骨架的潜力。
