Boc-Cys(Trt)-OH

Boc-Cys(Trt)-OH

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nalpha-9-fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side-chain and backbone anchoring strategies, and compatible protection for N-terminal cysteine.[Pubmed:15787970]

J Pept Res. 2005 Mar;65(3):395-410.

Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C-terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N(alpha)-9-fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N(alpha)-t-butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side-chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N-terminal cysteine residue have been developed: (i) incorporation of N(alpha)-9-fluorenylmethoxycarbonyl-S-(N-methyl-N-phenylcarbamoyl)sulfenylcystein e [Fmoc-Cys(Snm)-OH], allowing creation of an otherwise fully protected resin-bound intermediate with N-terminal free Cys; (ii) incorporation of N(alpha)-9-fluorenylmethoxycarbonyl-S-triphenylmethylcysteine [Fmoc-Cys(Trt)-OH], generating a stable Fmoc-Cys(H)-peptide upon acidolytic cleavage; and (iii) incorporation of N(alpha)-t-butyloxycarbonyl-S-fluorenylmethylcysteine [Boc-Cys(Fm)-OH], generating a stable H-Cys(Fm)-peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C-termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on-resin, as well as in solution after cleavage/purification.

Cysteine-S-trityl a key derivative to prepare N-methyl cysteines.[Pubmed:18020422]

J Comb Chem. 2008 Jan-Feb;10(1):69-78.

S-Trt Cys are used as precursors for the synthesis of protected NMe-Cys. N-Methylation of Alloc-Cys(Trt)-OH and Boc-Cys(Trt)-OH gives the corresponding N-methylated derivatives in good yields and purities, which can be further derivatized in solution to obtain a myriad of S-protected derivatives. To further broaden the scope of this methodology, the N (alpha)-amino protecting group of the NMe- S-protected Cys can be replaced easily either on the solid phase (from the Alloc precursor) or in solution (from the Boc precursor). Thus, this convenient route allows us to obtain many different protected NMe-Cys, which were of limited accessibility until now.

Synthesis and acid ionization constants of cyclic cystine peptides H-Cys-(Gly)n-Cys-OH (n = 0-4).[Pubmed:2599775]

Int J Pept Protein Res. 1989 Oct;34(4):346-51.

Cyclic peptide disulfides of the general formula H-Cys-(Gly)n-Cys-OH (n = 0-4) were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-n-Cys(Trt)-OBut] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK1 = 2.35-2.84) and to terminal amino group (pK2 = 5.61-6.93); pK1 values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK2 values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO- ----NH+3-) formation.

Protection of asparagine and glutamine during N alpha-Bpoc-based solid-phase peptide synthesis.[Pubmed:8740971]

Int J Pept Protein Res. 1996 Mar;47(3):209-13.

In this paper we describe the synthesis and properties of Bpoc-Asn(Trt)-OH, Bpoc-Asn(Trt)-OPfp, Bpoc-Gln(Trt)-OH and Bpoc-Gln(Trt)-OPfp. These derivatives are highly soluble in CH2Cl2 and can be coupled efficiently in solid-phase peptide synthesis. The peptides, acetyl-Ala-Phe-Asn(Trt)-Gly-Leu-Ala-O-Dbf-SH and Boc-Cys(Acm)-Ala-Phe-Gln(Trt)-Gly-Leu-Ala-O-Dbf-SH (where O-Dbf-SH is the peptide ester of 4-mercapto-6-hydroxydibenzofuran) were synthesized by stepwise solid-phase peptide synthesis using N alpha-Bpoc amino acids. We have observed that less than 0.1% of the trityl group is removed from the carboxamide of Gln and Asn during a standard 15 min N alpha-Bpoc deprotection in 0.5% TFA in CH2Cl2.