Synthesis of cyclic peptides and peptide libraries on a new disulfide linker.
A new cysteine-based disulfide linker for Fmoc solid phase peptide synthesis was developed (Fmoc-Cys(3-mercapto-3-methylbutanoic acid)OPp) that allows the on-resin assembly and side chain deprotection of cyclic peptides. Model peptides and a cyclic peptide library of the structure [a-a-x-x-a-a-c] composed of D-amino acids were assembled and the synthesis and cleavage conditions studied. The best cyclization results were obtained with PyBOP/HOAt/diisopropylethyl amine. Racemization rates of the cysteine in the analyzed model sequences were between 5.2 and 12.3%. Cleavage of the disulfide bond was best carried out with DTT in 50% 2-propanol/100 mM ammonium bicarbonate. The cleaved peptides can be used directly in biological assays.
Tegge
Werner
W
Helmholtz Centre for Infection Research, Department of Chemical Biology, D-38124 Braunschweig, Germany. werner.tegge@helmholtz-hzi.de
Bautsch
Wilfried
W
Frank
Ronald
R
D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis*
C524811:9-fluorenylmethoxycarbonyl-cysteinyl(3-mercapto-3-methylbutanoic acid) 2-phenyl-2-propyl ester; D019151:Peptide Library; D010456:Peptides, Cyclic; D003545:Cysteine