2024-03-29T09:01:14Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:02003916
2023-07-07T00:22:40Z
1903:1904:1905
Recent Advances in the Solid- and Solution-Phase Synthesis of Peptides and Proteins Using Microflow Technology
Masui, Hisashi
Fuse, Shinichiro
open access
This document is the Accepted Manuscript version of a Published Work that appeared in final form in [Organic Process Research & Development], copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [https://pubs.acs.org/articlesonrequest/AOR-FVWUB5WEN2TJTFWIFQED].”
microflow
α-peptides
N-methylated peptides
β-peptides
cyclic peptides protein
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.
ACS Publications
2023-06-17
2022-06-17
eng
journal article
AM
http://hdl.handle.net/2237/0002003916
https://nagoya.repo.nii.ac.jp/records/2003916
https://doi.org/10.1021/acs.oprd.2c00074
1083-6160
Organic Process Research & Development
26
6
1751
1765
https://nagoya.repo.nii.ac.jp/record/2003916/files/OPRD_final_version_manuscript.pdf
application/pdf
1.9 MB
2023-06-17