Biomimetic selenocystine based dynamic combinatorial chemistry for thiol-disulfide exchange

Dynamic combinatorial chemistry applied to biological environments requires the exchange chemistry of choice to take place under physiological conditions. Thiol-disulfide exchange, one of the most popular dynamic combinatorial chemistries, usually needs long equilibration times to reach the required equilibrium composition. Here we report selenocystine as a catalyst mimicking Nature’s strategy to accelerate thiol-disulfide exchange at physiological pH and low temperatures. Selenocystine is able to accelerate slow thiol-disulfide systems and to promote the correct folding of an scrambled RNase A enzyme, thus broadening the practical range of pH conditions for oxidative folding. Additionally, dynamic combinatorial chemistry target-driven self-assembly processes are tested using spermine, spermidine and NADPH (casting) and glucose oxidase (molding). A non-competitive inhibitor is identified in the glucose oxidase directed dynamic combinatorial library.

Nucleophilic catalysis of p-substituted aniline derivatives in acylhydrazone formation and exchange

Hydrazone bond formation is a versatile reaction employed in several research fields. It is one of the most popular reversible reactions in dynamic combinatorial chemistry. Under physiological conditions, hydrazone exchange...

Disulfide Metathesis via Sulfur…Iodine Interaction and Photoswitchability

The idea of constitutional dynamic chemistry (CDC) and dynamic combinatorial chemistry (DCC) is widespread in literature using the chemistry of disulfides. The synthesis of unsymmetrical diaryl disulfides is challenging due...

Hit-optimization using target-directed dynamic combinatorial chemistry: Development of inhibitors of the anti-infective target 1-deoxy-D-xylulose-5-phosphate synthase

Target-directed dynamic combinatorial chemistry (tdDCC) enables identification, as well as optimization of ligands for un(der)explored targets such as the anti-infective target 1-deoxy-D-xylulose-5-phosphate synthase (DXPS). We report the use of tdDCC...