1353048-75-5Relevant academic research and scientific papers
Studies towards enzymatic kinetic resolutions of 1,3-diol peptidomimetics obtained via the Ugi reaction
Klossowski, Szymon,Redzej, Adam,Szymkuc, Sara,Ostaszewski, Ryszard
, p. 134 - 143 (2013/09/12)
Enzymatic methods in combination with the multicomponent Ugi condensation make a very efficient method for simple synthesis of non-racemic peptidomimetics. The aim of the studies was to develop an enzymatic kinetic resolution of 1,3-diol peptidomimetics providing nonracemic compounds. Among many applications, 1,3-diols can serve as intermediates in the synthesis of anticancer agents - β-acyloxymethacrylic amides. Stereoselective enzymatic acylation and hydrololysis of Ugi products were investigated. The enantiomeric or diastereomeric excesses were determined in both cases. As a result, an efficient enzymatic method for the synthesis chiral, non-racemic 1,3-diol peptidomimetics was developed. ARKAT-USA, Inc.
Studies toward novel peptidomimetic inhibitors of thioredoxin-thioredoxin reductase system
K?ossowski, Szymon,Muchowicz, Angelika,Firczuk, Ma?gorzata,?wiech, Marta,Redzej, Adam,Golab, Jakub,Ostaszewski, Ryszard
, p. 55 - 67 (2012/02/15)
Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-κB and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.
