Evaluation of the trifluoromethanosulfonic acid/trifluoroacetic acid/thioanisole cleavage procedure for application in solid-phase peptide synthesis

Evaluation of the trifluoromethanosulfonic acid/trifluoroacetic acid/thioanisole cleavage procedure for application in solid-phase peptide synthesis

Autor Jubilut, Guita Nicolaewsky Autor UNIFESP Google Scholar
Cilli, Eduardo Maffud Autor UNIFESP Google Scholar
Tominaga, Mineko Autor UNIFESP Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Okada, Yoshio Google Scholar
Nakaie, Clovis Ryuichi Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Kobe Gakuin Univ
Resumo As an extension of our investigation of peptidyl-resin linkage stability towards different cleavage procedures used in the solid-phase peptide synthesis (SPPS) technique, the present paper evaluated the trifluoromethanesulfonic acid (TFMSA)/trifluoroacetic acid (TFA)/thioanisole method, varying the type of resin (benzhydrylamine-resin, BHAR; methylbenzhydrylamine-resin, MBHAR and 4-(oxymethyl)-phenylacetamidomethyl-resin, PAMR) and peptide resin-bound residue (Gly and Phe). the vasoactive angiotensin II (AII, DRVYIHPF) and its /Gly(8)/-AII analogue linked to those resins used routinely in tert-butyloxycarbonyl (Boc)-SPPS chemistry were submitted comparatively to a time course study towards TFMSA/TFA cleavage. At VC, /Gly(8)/-AII was completely removed from all resins in less than 6 h, but the hydrophobic Plies moiety-containing All sequence was only partially cleaved (not more than 15%) from BHAR or MBHAR in this period. At 25 degreesC, /Gly(8)/-AII cleavage time decreased to less than 2 h irrespective of the solid support. and quantitative removal of All from PAMR and MBHAR occurred in less than 3 h. However, about 10-15 h seemed to be necessary for cleavage of All from BHAR, and in this extended cleavage reaction a significant increase in peptide degradation rate was observed. Regardless of the cleavage temperature used, the decreasing order of acid stability measured for resins was BHAR > MBHAR > PAMR. Collectively, these findings demonstrated the feasibility of applying TFMSA/TFA solution as a substitute for anhydrous HF at the cleavage step in Boc-SPPS methodology. Care should be taken however, as the cleavage efficacy depends on multiple factors including the resin, peptide sequence. the time and temperature of reaction.
Palavra-chave peptide synthesise
peptidyl-resin cleavage
trifluoromethanesulfonic acid
4-(oxymethyl)-phenylacetamidomethyl-resin
benzhydrylamine-resin
methylbenzhydrylamine-resin
Idioma Inglês
Data de publicação 2001-09-01
Publicado em Chemical & Pharmaceutical Bulletin. Tokyo: Pharmaceutical Soc Japan, v. 49, n. 9, p. 1089-1092, 2001.
ISSN 0009-2363 (Sherpa/Romeo, fator de impacto)
Publicador Pharmaceutical Soc Japan
Extensão 1089-1092
Fonte http://dx.doi.org/10.1248/cpb.49.1089
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000170736600008
Endereço permanente http://repositorio.unifesp.br/handle/11600/26617

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