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

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概要

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• Ideally, the solid support used for tert-butyloxycarbonyl (Boc)-peptide synthesis method must allow sufficient stability of the peptide linkage towards TFA-α-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)≅4-(oxymethyl)-phenylacetamidomethyl-resin (PAMR)>chloromethyl-resin (CMR) and Phe>Gly≅His≅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 hydrophobic. 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.

• 公益社団法人日本薬学会の論文
• 1999-11-15

著者

• OKADA Yoshio

  Faculty of Pharmaceutical Sciences, Kobe Gakuin University

• MIRANDA ANTONIO

  Department of Biophysics, Escola Paulista de Medidna

• Miranda Antonio

  Department Of Biophysics Universidade Federal De Sao Paulo

• Okada Yoshio

  Faculty Of Pharmaceutical Sciences Kobe Gakuin University

• Miranda Antonio

  Department Of Biophysics Escola Paulista De Medidna

• JUBILUT Guita

  Department of Biophysics, Universidade Federal de Sao Paulo

• TOMINAGA Mineko

  Department of Biophysics, Universidade Federal de Sao Paulo

• NAKAIE Clovis

  Department of Biophysics, Universidade Federal de Sao Paulo

• MIRANDA Maria

  Department of Biochemistry, Chemistry Institute, Universidade de Sao Paulo

• Jubilut Guita

  Department Of Biophysics Universidade Federal De Sao Paulo

• Miranda Maria

  Department Of Biochemistry Chemistry Institute Universidade De Sao Paulo

• Nakaie Clovis

  Department Of Biophysics Universidade Federal De Sao Paulo

• Tominaga M

  Department Of Biophysics Universidade Federal De Sao Paulo

• Tominaga Mineko

  Department Of Biochemistry Institute Of Chemistry University Of Sao Paulo

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