Addition of HOXt (X = A or B) improves the efficiency of phenol-based coupling reagents during peptide synthesis |
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Authors: | Ayman El-Faham |
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Institution: | (1) Faculty of Science, Department of Chemistry, University of Alexandria, Ibrahimia, PO Box 426, 21321 Alexandria, Egypt |
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Abstract: | Summary In the course of comparing the effectiveness of HATU, HBTU, and phenol-based coupling reagents, such as the pentafluorophenyl,
2-nitrophenyl, and 2,4,5-trichlorophenyl uronium salts by (a) formation of Fmoc-Ala-Val-OtBu, (b) (2+1) segment coupling and (c) stepwise solid phase peptide assembly of typical model peptides such as the pentapeptide
H-Tyr-Aib-Aib-Phe-Leu-NH2 and ACP decapeptide (65–74), we found a striking improvement of the less effective phenol-based coupling reagents (HPyOPfp,
HPyONp, and HPyOTcp), both with regard to reaction rate and extent of epimerization, when HOAt was added and a clear superiority
of HAPyU (in the presence and absence of HOAt) relative to the compounds derived from HOBt, HOPfp, HONp, and HOTcp.
Abbreviations: Aib, α-aminoisobutyric acid; DIEA, diisopropylethylamine; TMP, collidine, 2,4,6,-tri-methylpyridine; DMF, N, N-dimethylformamide;
HOBt, 1-hydroxybenzotriazole; HOAt, 7-aza-1-hydroxybenzotriazole; HAPyU, 1-(1-pyrrolidinyl-1H-1,2,3-triazolo4,5-b]pyridin-1-ylmethylene)-N-methylmethanaminium
hexafluorophosphate N-oxide; HOPfp, pentafluorophenol; HONp, 2-nitrophenol; HOTcp, 2,4,5-trichlorophenol; HPyOPfp,bis(tetramethylene)pentafluorophenoxyformamidinium hexafluorophosphate; HpyONp,bis(tetramethylene)-2-nitrophenoxyformamidinium hexafluorophosphate; HPyOTcp,bis(tetramethylene)-2,4,5-trichlorophenoxyformamidinium hexafluorophosphate; BTCFHbis(tetramethylene)chloroformamidinium hexafluororophosphate. Amino acids and peptides are abbreviated and designated following
the rules of the IUPAC-IUB Commission of Biochemical Nomenclature J. Biol. Chem., 247 (1972) 977] |
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Keywords: | epimerization phenol-base coupling reagent solid phase peptide assembly |
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