The Reaction of Cysteine with Acetone. A Note on the Titration of Cysteine by the Acetone—Hydrochloric Acid Method of Linderstrˇom-Lang

Woodward, Gladys E.; Schroeder, E. F.

doi:10.1021/ja01288a037

Cited by 43 publications

(14 citation statements)

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“…Synthesis and characterization of the thiofunctional cysteine derivative have been done as reported in detail elsewhere. 28 In brief, literature-known formation of the HCl-salt of Tz4CA by treatment of l -cysteine hydrochloric salt with acetone 34 was performed first, followed by formylation of the amine according to literature. 35 Subsequently, the carboxylic functionality was mildly activated using N , N -carbonyldiimidazole in chloroform for 2 h at room temperature under an inert atmosphere.…”

Section: Resultsmentioning

confidence: 99%

Side-Chain Cysteine-Functionalized Poly(2-oxazoline)s for Multiple Peptide Conjugation by Native Chemical Ligation

et al. 2015

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We prepared statistical copolymers composed of 2-methyl-2-oxazoline (MeOx) in combination with 2-butenyl-2-oxazoline (BuOx) or 2-decenyl-2-oxazoline (DecOx) as a basis for polymer analogous introduction of 1,2-aminothiol moieties at the side chain. MeOx provides hydrophilicity as well as cyto- and hemocompatibility, whereas the alkene groups of BuOx and DecOx serve for functionalization with a thiofunctional thiazolidine by UV-mediated thiol–ene reaction. After deprotection the cysteine content in functionalized poly(2-oxazoline) (POx) is quantified by NMR and a modified trinitrobenzenesulfonic acid assay. The luminescent cell viability assay shows no negative influence of cysteine-functionalized POx (cys-POx) concerning cell viability and cell number. cys-POx was used for multiple chemically orthogonal couplings with thioester-terminated peptides through native chemical ligation (NCL), which was performed and confirmed by NMR and MALDI-ToF measurements.

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Section: Resultsmentioning

confidence: 99%

Side-Chain Cysteine-Functionalized Poly(2-oxazoline)s for Multiple Peptide Conjugation by Native Chemical Ligation

et al. 2015

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“…In spite of a literature report on the reversible formation of thiazolidines under basic conditions,8 this transformation has not been previously reported as useful for DCC. 4-Carboxyl ethyl-2-arylthiazolidines can be readily obtained by condensation of aldehydes ( 1 ) and cysteine ethyl ester ( 2 ) in EtOH at room temperature (Scheme 1).…”

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confidence: 88%

Reversible Thiazolidine Exchange: A New Reaction Suitable for Dynamic Combinatorial Chemistry

et al. 2009

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New dynamic combinatorial libraries (DCLs) were generated using the reversible aminothiol exchange reaction of thiazolidines and aromatic aldehydes. The reaction proceeded in aqueous buffered media at pH 4 and room temperature to generate thermodynamically controlled mixtures of heterocycles. The synthesis of an enantiomerically pure thiazolidinyloxazolidine is also reported. The oxazolidine moiety could be exchanged in CH 2 Cl 2 in the presence of catalytic p-TsOH.Dynamic combinatorial chemistry (DCC) has considerable potential in the discovery of small molecule ligands for artificial receptors and large biomolecules. DCC is largely based on the use of reversible reactions to generate compound mixtures -Dynamic Combinatorial Libraries (DCLs) -that are in thermodynamic equilibrium. The composition of the library is determined by the properties of each of the library members under the particular conditions of the experiment; this equilibrium is likely to respond to the presence of a template or another change in the environment. 1 The covalent reversible reactions usable in DCC are relatively rare compared to the irreversible processes favored in traditional synthetic chemistry, and most of the former involve carbonyl compounds, imines and acetals.Four different types of substrates have previously been used to generate DCLs from carbonyl compounds by acetal exchange (Figure 1) The acid-catalyzed transacetylation of thiazolidines and related compounds attracted our closer attention as a possible extension of the latter heterocycle formation process.Thiazolidines 3 were selected as simple models in order to identify equilibration conditions for DCL formation. In spite of a literature report on the reversible formation of thiazolidines under basic conditions, 8 this transformation has not been previously reported as useful for DCC. 4-Carboxyl ethyl-2-arylthiazolidines can be readily obtained by condensation of aldehydes (1) and cysteine ethyl ester (2) in EtOH at room temperature (Scheme 1).The discovery of new reversible reactions compatible with an aqueous enviroment is an important objective for the use of biomolecules as templates in DCLs. We screened different aqueous conditions, with variations in pH and reaction time, in order to establish optimal thermodynamic exchange conditions for the thiazolidine exchange. The reaction of 3a with equimolar amounts of p-Cl-benzaldehyde (1b) at room temperature was used as a reference (Table 1).Thermodynamic equilibration of a mixture of 3a and 1b occurred at pH 4 over 24 to 48 h at room temperature. 9 After 3 d, heterocycles 3a and 3b were stable in the aqueous environment and thiazolidines (90-98%) and ester 2 (2-10%) were recovered (entries 1, 2 and 3). Equilibration at pH 5 was slower, but after 3 d, the ratio indicated that equilibrium was reached (entries 4, 5 and 6). Equilibration at pH 6 was not complete after 3 d at rt (entries 7, 8 and 9). Equilibration at pH 7 did not proceed during 3 d at rt (entry 10) and the presence of ester 2 was not detected. The m...

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“…This connects the reactive thiol group via a stable amide bond with the protected cysteine. In the first step, literature known 2,2‐dimethylthiazolidine‐4‐carboxylic acid hydrochloric salt was obtained by treating L‐cysteine hydrochloric salt (Figure A) with acetone concurrently protecting the thiol and the amine of cysteine . A second protection of the thiazolidine amine was necessary to prevent side reaction upon activation of the carboxyl group.…”

Section: Resultsmentioning

confidence: 99%

Cysteine‐Functional Polymers via Thiol‐ene Conjugation

Kuhlmann

Reimann

Hackenberger

et al. 2015

Macromol. Rapid Commun.

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A thiofunctional thiazolidine is introduced as a new low-molar-mass building block for the introduction of cysteine residues via a thiol-ene reaction. Allyl-functional polyglycidol (PG) is used as a model polymer to demonstrate polymer-analogue functionalization through reaction with the unsaturated side-chains. A modified trinitrobenzenesulfonic acid (TNBSA) assay is used for the redox-insensitive quantification and a precise final cysteine content can be predetermined at the polymerization stage. Native chemical ligation at cysteine-functional PG is performed as a model reaction for a chemoselective peptide modification of this polymer. The three-step synthesis of the thiofunctional thiazolidine reactant, together with the standard thiol-ene coupling and the robust quantification assay, broadens the toolbox for thiol-ene chemistry and offers a generic and straightforward approach to cysteine-functional materials.

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The Reaction of Cysteine with Acetone. A Note on the Titration of Cysteine by the Acetone—Hydrochloric Acid Method of Linderstrˇom-Lang

Cited by 43 publications

References 0 publications

Side-Chain Cysteine-Functionalized Poly(2-oxazoline)s for Multiple Peptide Conjugation by Native Chemical Ligation

Side-Chain Cysteine-Functionalized Poly(2-oxazoline)s for Multiple Peptide Conjugation by Native Chemical Ligation

Reversible Thiazolidine Exchange: A New Reaction Suitable for Dynamic Combinatorial Chemistry

Cysteine‐Functional Polymers via Thiol‐ene Conjugation

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