Peptides have become increasingly important as drugs and drug candidates. In particular, specialty peptides have garnered considerable attention in recent years because of their improved metabolic stability, higher affinity, and biological target selectivity; some of them have the ability to enable cell membrane permeation and oral administration. Despite its long history, peptide synthesis has various limitations, such as high cost, generation of large amounts of waste, and the requirement for hazardous reagents and solvents. Microflow synthesis, wherein the inner diameter of the reaction tube is ≤1 mm, presents several advantages compared with conventional batch synthesis, such as precise control of the reaction time on a short scale, precise reaction temperature control, and facile scale-up with high reproducibility. Microflow technology has been utilized for peptide synthesis since the beginning of the 21st century. The advantages of microflow synthesis enable the use of highly active and unstable chemical species or high-temperature conditions that accelerate peptide synthesis. The combined use of microflow technology, automated synthesis, and online monitoring technologies has emerged in recent years. This approach not only improved the synthetic efficiency but also afforded large amounts of reliable data that can be used to train machine learning models. This review summarizes the solid- and solution-phase syntheses of α-peptides and specialty peptides, including N-methylated peptides, β-peptides, and cyclic peptides, reported mainly after 2017. The recently reported mesoflow peptide syntheses (inner diameter of the reaction channels > 1 mm), the microflow automated syntheses, and in-line analysis are covered in this review.

中文翻译：

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使用微流技术固相和溶液相合成肽和蛋白质的最新进展

肽作为药物和候选药物变得越来越重要。尤其是近年来，特种多肽因其改善的代谢稳定性、更高的亲和力和生物靶点选择性而备受关注。其中一些具有使细胞膜渗透和口服给药的能力。尽管其历史悠久，但肽合成具有各种局限性，例如成本高、产生大量废物以及需要危险的试剂和溶剂。反应管内径≤1mm的微流合成与传统的间歇合成相比，具有在短时间内精确控制反应时间、精确控制反应温度、易于放大、快速放大等优点。再现性。自 21 世纪初以来，微流技术已被用于肽合成。微流合成的优势使得能够使用高活性和不稳定的化学物质或加速肽合成的高温条件。近年来出现了微流技术、自动合成和在线监测技术的结合使用。这种方法不仅提高了合成效率，而且提供了大量可靠的数据，可用于训练机器学习模型。本综述总结了主要在 2017 年以后报道的 α-肽和特种肽的固相和液相合成，包括 N-甲基化肽、β-肽和环肽。最近报道的中流肽合成（反应的内径通道 > 1 毫米），