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  5. Greening the solid-phase peptide synthesis process. 2-MeTHF for the incorporation of the first amino acid and precipitation of peptides after global deprotection
 
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Greening the solid-phase peptide synthesis process. 2-MeTHF for the incorporation of the first amino acid and precipitation of peptides after global deprotection
File(s)
10.1021@acs.oprd.8b00335.pdf (10.76 MB)
Accepted version
Author(s)
Al Musaimi, Othman
Jad, Yahya E
Kumar, Ashish
El-Faham, Ayman
Collins, Jonathan M
more
Type
Journal Article
Abstract
In solid-phase peptide synthesis, dichloromethane is the predominant solvent used to incorporate the first amino acid on a 2-chlorotrityl chloride resin (via nucleophilic substitution) and Wang resin (via activation with carbodiimide in the presence of 4-dimethylaminopyridine). However, legal authorities have restricted the use of this solvent, as it is considered hazardous and a potential occupational carcinogen. Therefore, there is a need for an alternative that is easy to handle and poses less risk for the environment and more importantly for human health. Herein, we describe 2-methyltetrahydrofuran as a greener alternative for the incorporation of the first protected amino acids on both 2-chlorotrityl chloride and Wang resins. The amounts of several amino acids loaded on 2-chlorotrityl chloride and Wang resins using dry dichloromethane or 2-methyltetrahydrofuran were comparable. In addition, the use of 2-methyltetrahydrofuran rendered acceptable racemization and dipeptide formation in the case of Wang resin. This solvent can also be used to replace diethyl ether and tert-butyl methyl ether in the peptide precipitation step performed after final global deprotection. On the basis of our findings, 2-methyltetrahydrofuran emerges as a good alternative to the hazardous solvents currently used for amino acid incorporation and peptide precipitation. Furthermore, taking into account that 2-methyltetrahydrofuran proved effective for the elongation of the peptide in a solid-phase mode, we propose 2-methyltetrahydrofuran as a universal solvent for all solid-phase peptide synthesis steps, namely, incorporation of the first amino acid, assembly of the peptide chain, and precipitation of the final peptide.
Date Issued
2018-12-01
Date Acceptance
2018-11-21
Citation
Organic Process Research and Development, 2018, 22 (12), pp.1809-1816
URI
http://hdl.handle.net/10044/1/88628
DOI
https://www.dx.doi.org/10.1021/acs.oprd.8b00335
ISSN
1083-6160
Publisher
American Chemical Society
Start Page
1809
End Page
1816
Journal / Book Title
Organic Process Research and Development
Volume
22
Issue
12
Copyright Statement
© 2018 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.oprd.8b00335
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000454568200027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Physical Sciences
Chemistry, Applied
Chemistry, Organic
Chemistry
2-MeTHF
incorporation
precipitation
solid-phase peptide synthesis
racemization
dipeptide formation
CYCLOPENTYL METHYL-ETHER
2-CHLOROTRITYL CHLORIDE
SOLVENT
2-METHYLTETRAHYDROFURAN
CATALYSTS
SUPPORTS
PROTEIN
RESIN
Publication Status
Published
Date Publish Online
2021-11-21
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