Chemoselective Protection of Glutathione in the Preparation of Bioconjugates: The Case of Trypanothione Disulfide

Abstract

A novel synthetic route to the chemoselectively protected N,S-ditritylglutathione monomethyl ester is described involving the chemical modification of the commercially available glutathione (GSH). The synthetic value of this building block in the facile preparation of GSH bioconjugates in a satisfying overall yield was exemplified by the case of trypanothione disulfide (TS2), a GSH-spermidine bioconjugate, involved in the antioxidative stress protection system of parasitic protozoa, such as trypanosoma and leishmania parasites.

Synthesis of Protected 3,4- and 2,3-Dimercaptophenylalanines as Building Blocks for Fmoc-Peptide Synthesis and Incorporation of the 3,4-Analogue in a Decapeptide Using Solid-Phase Synthesis

“…Moreover, the dithiol function can be regenerated upon treatment with an excess of iodine. Using commercially available toluene-3,4-dithiol (2), we attempted the protection of dithiolene with Acm groups (Scheme 1, pathways a and b). Following a reported procedure, 9 the deprotected compound (3) was obtained in a moderate 45% yield.…”

“…13 C{ 1 H} NMR (75 MHz, CDCl 3 ): δ 169. 2,167.4,143.1,138.2,136.9,133.5,128.2,128.0,127.6,123.6,122.1,78.3,67.2,62.8,37.5,23.1,14.1 ppm. IR (neat): ν max 3405,3064,2983,1740,1680,1493,1443,1276,1198,696 Na, 558.1385;found, 558.1387.…”

“…1 The ability of the thiol group to form reversible disulfide bridges confers to cysteine a key role in the conformational structure of peptides or proteins. 2 Over the past several decades, cysteine is also very often used in the thioester method for the chemical synthesis of peptides and proteins through native chemical ligation (NCL) as well as for their selective modification. 3 On the other hand, the nucleophilicity of its conjugated base (cysteinate) endows proteins containing cysteines with special functional properties.…”

Water Contaminated by Industrial Textile Dye: Study on Decolorization Process

“…High-Resolution Nuclear Magnetic Resonance analysis (HR-NMR) methods used for the structural determination of organic compounds in complex mixtures [87,88] were also applied on samples of the starting water solutions and the resulting solutions obtained from the photodegrading process, in order to assess the efficiency of the UV treatment. NMR experiments were performed with a Bruker Advance AC300 instrument, by fixing the probe temperature at 25 • C. Samples (480 µL) of the aqueous solutions were spiked with a small amount of DMSO-d 6 (20 µL) as the spectral calibrating agent.…”

2,3-Diaminopropanols Obtained from d-Serine as Intermediates in the Synthesis of Protected 2,3-l-Diaminopropanoic Acid (l-Dap) Methyl Esters

“…The aqueous phase was washed with small portions of AcOEt (3 × 10 mL), treated with 5% aqueous KHSO 4 (10 mL), and re-extracted with AcOEt (3 × 10 mL). The organic layers were dried over MgSO 4 and paper-filtered, and the solvent was evaporated to dryness, yielding a raw material which was directly treated with an excess of diazomethane (0.66 N solution in dry DCM, 4 mL), under magnetic stirring for 15 min at room temperature [85] Step 1: Acidolysis. To a solution of 4 (229 mg, 0.5 mmol), in dry DCM (3 mL), TFA (2 mL) and TFE (0.3 mL) were added.…”