Resin selection based on the lability of peptidyl-resin linkage towards HF and TFA steps: Dependence on the C-terminal amino acid and peptide length

Resin selection based on the lability of peptidyl-resin linkage towards HF and TFA steps: Dependence on the C-terminal amino acid and peptide length

Author Jubilut, Guita Nicolaewsky Autor UNIFESP Google Scholar
Miranda, Maria Teresa Google Scholar
Tominaga, Mineko Google Scholar
Okada, Yoshio Google Scholar
Miranda, Antonio de Autor UNIFESP Google Scholar
Nakaie, Clovis Ryuichi Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Kobe Gakuin Univ
Abstract Ideally, the solid support used for teut-butyloxycarbonyl (Boc)-peptide synthesis method must allow sufficient stability of the peptide linkage towards TFA-alpha-amino deprotection but adequate lability to final HF cleavage. Due to these conflicting characteristics, the choice of the correct resin for peptide synthesis is complex and dependent upon many factors. Aiming to clarify this issue, a time-course study of the trifluoroacetic acid (TFA) and HF steps using model peptidyl-resins was developed. The peptidyl-resin bond stability was strongly dependent upon the resin and the carboxy-terminus residue, The decreasing order of acid stability for resins was: benzhydrylamine-resin (BHAR)>p-methylbenzhydrylamine-resin (MBHAR)congruent to 4-(oxymethyl)-phenylacetamidomethyl-resin (PAMR)>chloromethyl-resin (CMR) and Phe>Gly congruent to His congruent to Asp for C-terminal amino acids. HF-cleavage times of near 6 h (BHAR) and 2-3 h (MBHAR and PAMR) were necessary for quantitative cleavage of hydrophobic Phe residue-containing sequence at its C-terminal portion. When premature chain loss in TFA and incomplete cleavage in HF values were both quantitatively considered, a significant decrease in the overall yield (up to 35%) was observed in some resins, Moreover, MBHAR was more suitable than BHAR only when the peptide C-terminal residue is hydrophohic. The data also allow the prediction that due to more significant chain loss in TFA when MBHAR is used, BHAR will be the resin of choice for much longer than 40-mer peptide sequences containing C-terminal hydrophilic residues. Otherwise PAMR is the best resin for the synthesis of free carboxyl peptides but significantly low HF cleavage was observed when the C-terminal amino acid is of the hydrophobic-type.
Keywords peptide synthesis
peptidyl-resin cleavage
benzhydrylamine-resin
methylbenzhydrylamine-resin
Language English
Date 1999-11-01
Published in Chemical & Pharmaceutical Bulletin. Tokyo: Pharmaceutical Soc Japan, v. 47, n. 11, p. 1560-1563, 1999.
ISSN 0009-2363 (Sherpa/Romeo, impact factor)
Publisher Pharmaceutical Soc Japan
Extent 1560-1563
Origin http://doi.org/10.1248/cpb.47.1560
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000083814900008
URI http://repositorio.unifesp.br/11600/43271

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account