Tryptophan 2-sulfenyl derivatives

N-Acetyl-tryptophan and indole-3-propionic acid have been labelled with deuterium and tritium by Spande and Fontana 371), who employed the corresponding 2-sulfenyl derivatives. The spirolactones (176) obtained from (175) by treatment with N-bromosuccinimide were reduced with NaBD4 or NaBTa in good yields back to the corresponding indole compounds specifically labelled with deuterium or tritium at the 2-position. The method seems to offer a new general procedure which permits introduction of label specifically at the 2-position of indoles bearing a propionic acid side chain at the 3-position. 

In the absence of efficient Nps-Q (92) capture, this intermediate reacts with the indole side chain of tryptophan residues to produce the related 2-Nps derivatives 96 (Scheme 48). Although reaction of sulfenyl hahdes with indoles was exploited by Wieland et al.t for the synthesis of phaUoidin, this side reaction leads to irreversible modification of Trp-containing peptides.This side reaction does not occur via an intramolecular electrophilic substitution as postulated previously,but by a direct attack of the Nps-Cl (92) in fact, it is efficiently suppressed by the addition of a large excess of an indole derivative as a scavenger.These scavengers serve also to decrease the proton activity of the acids vide supra). Due to the unpleasant odor of 2-methylindole the less volatile 1-acetyltryptophan butyl ester has been proposed as scavenger.f ... 

Other derivatives of tryptophan which may also be obtained after enzymic hydrolysis of derivatized proteins are those obtained by reaction with sulfenyl halides (Scoffone et al. 1968) and 2-hydroxynitro-benzyl bromide (Barman and Koshland 1967) ( 3.6.2). 

Site-specific sulfenylation of tryptophan residues in egg-white lysozyme has been attained by either limiting the amount of reagent, or modifying the reaction conditions. Thus, Trp-108 is the major site of modification upon addition of one equivalent of 2-thio-(2-nitro-4-carboxyphenyljsulfenyl chloride to lysozyme in 25% acetic acid (Veronese et al. 1972). Specific modification of Trp-62 was attained in approximately 8 hr by the addition of 5 consecutive portions of solid NPS-Cl (10 /imole for each ml of reaction mixture) to a solution of lysozyme (0.5 /imole/ml) in 0.1 M sodium acetate at pH 3.5 (Shechter et al. 1972). In both cases, the protein derivative was separated from other products, and unreacted enzyme by ion-exchange chromatography. 

Thioxindole-derivatives. Upon reaction of tryptophan or another indole with the bifunctional sulfenyl halide, sulfur dichloride, in glacial acetic acid, dimers are obtained with a disulfide bridge at the 2-position (149). By reduction with excess mercaptan (mercaptoethanol. 

Oxidation. Oxidation of an indole 2-thioether is of interest since this would increase the number of derivatives of tryptophan obtainable from the sulfenylation reaction, thus providing new permutations in the study of the structure-function relationships of tryptophan-containing peptides and proteins. In addition, the indole 2-sulfoxide function occurs naturally in the poisonous cyclic peptides amatoxins 114, 429). 

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