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N-(2-chlorobenzyloxycarbonyloxy)-succinimide as a terminating agent for solid-phase peptide synthesis: Application to a one-step purification procedure

✍ Scribed by Haydn L. Ball; Paolo Mascagni


Book ID
104630507
Publisher
Springer Netherlands
Year
1995
Tongue
English
Weight
559 KB
Volume
2
Category
Article
ISSN
1573-3149

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✦ Synopsis


The solid-phase synthesis of peptides is limited by the ability to separate the target sequence from chromatographically similar deletion and truncated impurities. Earlier we have reported the development of a one-step purification procedure for Boc-and Fmoc-synthesised peptides, which involves the incorporation of a base-labile probe with enhanced chromatographic properties at the N-terminal residue of the peptidyl-resin. To prevent the coderivatisation of deletion peptides, an efficient capping procedure is required at each step of chain assembly to terminate unreacted amino groups. N-(2-Chlorobenzyloxycarbonyloxy)-succinimide (Z(2-C1)-OSu) was found to be a highly effective capping agent for automated SPPS, because it is (i) a solid which can be dissolved when required to limit possible degradation; (ii) stable to the reagents commonly used for Boc/Fmoc chemistries; and (iii) sufficiently reactive so as not to significantly extend cycle times. We demonstrate the effectiveness of a 5 min capping cycle, using Z(2-C1)-OSu, by synthesising several peptides ranging from 12 to 101 residues in length, by both the Fmoc and Boc chemical strategies.