Coupling reagents play crucial roles in the iterative construction of amide bonds for the synthesis of peptides and peptide-based derivatives. The novel DIC/Oxyma condensation system featured with the low risk of explosion displayed remarkable abilities to inhibit racemization, along with efficient coupling efficiency in both manual and automated syntheses. Nevertheless, an ideal reaction molar ratio in DIC/Oxyma condensation system and the moderate reaction temperature by manual synthesis remain to be further investigated. Herein, the synthetic efficiencies of different reaction ratios between DIC and Oxyma under moderate reaction temperature were systematically evaluated. The robustness and efficiency of DIC/Oxyma condensation system are validated by the rapid synthesis of linear centipede toxin RhTx. Different folding strategies were applied for the construction of disulfide bridges in RhTx, which was further confirmed in assays of circular dichroism and patch-clamp electrophysiology evaluation. This work establishes the DIC/Oxyma-based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, the strategy presented here provides robust technical supports for the large-scale synthesis and oxidative folding of RhTx.

中文翻译：

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基于 DIC/Oxyma 的蜈蚣毒素 RhTx 加速合成和氧化折叠研究

偶联剂在用于合成肽和基于肽的衍生物的酰胺键的迭代构建中起着至关重要的作用。具有低爆炸风险的新型 DIC/Oxyma 缩合系统显示出显着的抑制外消旋化的能力，以及在手动和自动合成中的高效偶联效率。尽管如此，DIC/Oxyma 缩合体系的理想反应摩尔比和人工合成的适度反应温度仍有待进一步研究。在此，系统地评估了在中等反应温度下 DIC 和 Oxyma 之间不同反应比例的合成效率。通过线性蜈蚣毒素 RhTx 的快速合成验证了 DIC/Oxyma 缩合系统的稳健性和效率。不同的折叠策略被应用于 RhTx 中二硫键的构建，这在圆二色性和膜片钳电生理学评估中得到进一步证实。这项工作建立了在适度缩合条件下基于 DIC/Oxyma 的肽加速合成，这对于肽的手动合成特别有用。此外，这里提出的策略为 RhTx 的大规模合成和氧化折叠提供了强有力的技术支持。