The investigation of Fmoc-cysteine derivatives in solid phase peptide synthesis.
Fmoc-Cys(t-Bu)-OH, Fmoc-Cys(Acm)-OH, and Fmoc-Cys(Trt)-OH exhibit excellent synthesis characteristics when used in Fmoc solid phase peptide synthesis on the Applied Biosystems Model 431A peptide synthesizer. The actual 5% scavenger mixture will vary according to the particular amino acid residues present. As was previously mentioned, an anisole/ethanedithiol/ethylmethylsulfide mixture (3:1:1) works well as a general scavenger solution for TFA cleavage of Fmoc synthesized peptide resins. It also may be possible to use lower acid (TFA) concentrations. The syntheses and workups of the peptide Somatostatin utilizing these derivatives demonstrate the ease of using these cysteine derivatives with the Fmoc chemistry approach. The use of either the t-Bu or the Acm moiety produces a peptide containing protected thiol groups after cleavage with 95% TFA. The Fmoc-Cys(Trt)-OH derivative is efficiently deprotected using 95% TFA. This investigation should provide further insight into synthesis options and cleavage protocols when working with cysteine-containing peptides.
McCurdy
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Applied Biosystems, Inc., Foster City, CA 94404.
D000595:Amino Acid Sequence; D003545:Cysteine / Q000031:analogs & derivatives*; D005449:Fluorenes; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009555:Ninhydrin; D010455:Peptides / Q000138:chemical synthesis*; D013004:Somatostatin / Q000138:chemical synthesis*
D005449:Fluorenes; D007202:Indicators and Reagents; D010455:Peptides; C074730:N-(alpha)-fluorenylmethyloxycarbonyl-S-tritylcysteine; D013004:Somatostatin; C074728:N(alpha)-fluorenylmethyloxycarbonyl-S-tert-butylcysteine; C074729:N(alpha)-fluorenylmethyloxycarbonyl-S-acetamidomethylcysteine; D009555:Ninhydrin; D003545:Cysteine