Summary
This paper describes a novel solid phase peptide synthesis method for the systematic C-terminal modification of cysteine-containing peptides. In this method, cysteine is linked to chloromethylated polystyrene resin by its thiol functionality, followed by protection of the N-terminus and derivatization of the carboxylic acid to esters or amides. We report here on examples of the methodology and its application to the synthesis of Ac-Asp-cyclo(Cys-Gly-Pro-Cys)-NHBzl, a cyclic peptide amide. The method has been applied to the synthesis of complex esters as well as amides.
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Abbreviations
- Ac:
-
acetyl
- AcN:
-
acetonitrile
- Ac2O:
-
acetic anhydride
- AcOH:
-
acetic acid
- Boc:
-
t-butyloxycarbonyl
- BOP:
-
benzotriazol-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate
- Bzl:
-
benzyl
- cHex:
-
cyclohexyl
- DBU:
-
1,8-diazabicyclo[5.4.0]-undec-7-ene
- DCC:
-
N,N′-dicyclohexylcarbodiimide
- DCM:
-
dichloromethane
- DIEA:
-
diisopropylethylamine
- DMF:
-
dimethylformamide
- DMS:
-
dimethylsulfide
- HOB:
-
1-hydroxybenzotriazole
- MBzl:
-
4-methyl benzyl
- MeOH:
-
methanol
- TEA:
-
triethylamine
- TEAP:
-
triethylammonium phosphate
- TFA:
-
trifluoroacetic acid
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Delaet, N.G.J., Tsuchida, T. Convenient solid phase synthesis method for the preparation of cysteine C-terminally derivatized peptides. Lett Pept Sci 2, 325–331 (1996). https://doi.org/10.1007/BF00119995
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DOI: https://doi.org/10.1007/BF00119995