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9 p.-8 fig.-2 tab., Protein-directed dynamic combinatorial chemistry (P-D DCC) is considered a powerful strategy to identify ligands to pharmacologically relevant protein targets. The protein selects its affinity ligands in situ through a thermodynamic templated effect in which the library composition shifts to the formation of specific library members at the expense of other (nonbinding) species. The increase in concentration of the selected species is known as amplification and leads to the discovery of new hit compounds for protein targets. This Mini-Review contains an updated overview of the protein-directed DCC applications and the fundamental aspects to take into account when designing a P-D DCC experiment such as the most biocompatible reversible reactions and the methodology used to analyze the experiments., This work was supported by the grant PID2019-108587RB-I00 from the Spanish Ministry of Science and Innovation (MCI).

12 p.-9 fig., 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., This work was supported by the Spanish Ministry of Science and Innovation with Grant PID2019-108587RB-I00 (R.P.F.)