2-Chlorotrityl chloride resins, peptide

FIGURE 5.22 (A) Reaction of an Fmoc-amino acid with 2-chlorotrityl chloride resin.56 The ester bond formed is cleavable by the mild acid, which does not affect tert-butyl-based protectors. (B) Generation of a protected peptide containing cystine by detachment of a chain, deprotection of cysteine residues, and oxidation of the sulfhydryls by the reagent containing iodine. The cations produced are trapped by CF3CH2OH. 

K Barlos, O Chatzi, D Gatos, G Stavropoulus. 2-Chlorotrityl chloride resin. Studies on anchoring of Fmoc-amino acids and peptide cleavage. Int J Pept Prot Res 37,513,... 

As solid support use Rink-amide MBHA resin (0.6 mmol/g, 100-200 mesh, MultiSynTec, Bochum, Germany) to obtain C-terminal peptide amides and Wang-resin (1.2 mmol/g, 100-200 mesh, MultiSynTec) or 2-chlorotrityl chloride resin (1.5 mmol/g, 100-200 mesh, Novabiochem, Merck KGaA, Darmstadt, Germany) to produce C-terminal free acids. 

The preparation of protected peptides and their sequential condensation were done on the 2-chlorotrityl chloride resin (Fig. 1). 

Fig. l The use of the 2-chlorotrityl chloride resin for the preparation of protected peptides and proteins. Either amino acids (a) or fully protected peptide fragments (b) are condensed to the growing peptide chain on the resin. 

The fully protected peptides were synthesized either on a manual shaker or after optimization of coupling conditions [18] on an automatic peptide synthesizer (ACT 200) from Advanced Chemtech using the 2-chlorotrityl chloride resin and Fmoc/t-Butyl strategy [2]. The coupling with TBTU/DIEA [2] and the... 

Two trityl-based supports are presently in common use for the production of peptide adds by Fmoc SPPS 2-chlorotrityl chloride resin 7 (12) and 4-(chloro(diphenyl)methyl)benzoyl resin 8 (13). 

Chlorotrityl chloride resin is normally supphed with a displaceable chlorine content of 1.0-1.6 mmol/g. For the purposes of peptide synthesis, this substitution can sometimes be too high and can be reduced by treating the resin with a sub-stoichiometric amount of amino acid derivative and then capping imreacted sites with MeOH. 

To negate the need to use the harsh and potentially hazardous deprotection reagent hydrazine, a superior alternative, which is particularly compatible for use in Fmoc/rBu solid phase synthesis, is Af-Fmoc-hydroxylamine, which can be used to effect a nucleophilic displacement reaction of 2-chlorotrityl chloride resin (33) (Figure 9). The resultant N-Fmoc-aminooxy-2-chlorotrityl polystyrene resin can be used for the synthesis of peptide hydroxamates as described in Protocol 8. 

Synthesis of protected peptide fragments 2.2.1 Esterification of the first amino acid on 2-chlorotrityl chloride resin... 

Barlos, K., Chatzi, O., Gatos, D., and Stavropoulos, G. (1991) 2-Chlorotrityl chloride resin—Studies on Anchoring of Fmoc-Amino Acids and Peptide Cleavage. Int. J. Pept. Protein Res. 37,513-520. 

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