Abstract
Abstract A new basic α-amino acid with a quaternary ammonium side chain was synthesized in high yield by trimethylaminoethylation of l-cysteine with (2-bromoethyl)trimethylammonium (BETA) bromide at pH 9.1. The amino acid, l-[2-[(2-amino-2-carboxyethyl)thio]ethyl]trimethylammonium hydroxide, inner salt, is named 4-thialaminine or thialaminine. It was purified as crystals of bromide hydrobromide, bromide hydrobromide (2:1), and chloride hydrochloride. The N2-p-tolylsulfonyl derivative and esters of this derivative were also prepared. (2-Iodoethyl)trimethylammonium nitrate reacted nearly as rapidly as BETA bromide with cysteine, but (2-chloroethyl)trimethylammonium chloride reacted very slowly. Treatment of dithiothreitol-reduced proteins with BETA bromide resulted in quantitative conversion of cysteine residues to 4-thialaminine without significant reduction in content of other amino acid residues. Thialaminine was found to be extremely stable under the usual conditions of acid hydrolysis of proteins and eluted between lysine and histidine in the amino acid analyzer. In contrast to most products of reduction and alkylation or of S-sulfonation of proteins, reduced and trimethylaminoethylated proteins were readily soluble in water. Thialaminyl peptide bonds were resistant to the action of trypsin; on the other hand, the chymotryptic activity of trypsin toward certain bonds of trimethylaminoethylated insulin was enhanced.
Highlights
A new basic a-amino acid with a quaternary ammonium side chain was synthesized in high yield by trimethylaminoethylation of L-cysteine with (Z-bromoethyl)trimethylammonium (BETA) bromide at pH 9.1
[(2-amino-2-carboxyethyl)thio]ethyl]trimethylammonium hydroxide, inner salt, is named 4-thialaminine or thialaminine. It was purified as crystals of bromide hydrobromide, bromide hydrobromide (2: l), and chloride hydrochloride
Treatment of dithiothreitol-reduced proteins with BETA bromide resulted in quantitative conversion of cysteine residues to 4-thialaminine without significant reduction in content of other amino acid residues
Summary
A new basic a-amino acid with a quaternary ammonium side chain was synthesized in high yield by trimethylaminoethylation of L-cysteine with (Z-bromoethyl)trimethylammonium (BETA) bromide at pH 9.1. Treatment of dithiothreitol-reduced proteins with BETA bromide resulted in quantitative conversion of cysteine residues to 4-thialaminine without significant reduction in content of other amino acid residues. Several reactions for modification of sulfhydryls or disulfides to acidic or neutral groups are used in protein chemistry, the only modification to a basic group in common use is aminoethylation (2, 3). A stable basic amino acid, S-P-(4-pyridylethyl)cysteine,l was found to be the product of the reaction of 4-vinylpyridine with cyst,eine (4), and the product was shown to be useful in the determination of half-cystine content of proteins (5). In the present study the sulfhydryl group of cysteine and of cysteine residues in reduced proteins was alkylated with (2-bromoethyl)trimethylammonium bromide and with (2-iodoethyl)trimethylammonium nitrate to produce 4-. Product of the reaction of equivalent cysteine and (2-bromoethyl)trimethylammonium amounts bromide
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