MG-132 is a tripeptide aldehyde (Z-l-leu-l-leu-l-leu-H, 2) proteasome inhibitor that exerts antitumor activity and enhances cytostatic/cytotoxic effects of chemo- and radiotherapy. Because of a troublesome synthesis of tripeptides with a non-natural configuration and modified side chains of amino acids, only two stereoisomers of MG-132 have been reported. Here, we propose a new approach to the synthesis of tripeptide aldehydes based on the Ugi reaction. Chiral, enantiomerically stable 2-isocyano-4-methylpentyl acetates were used as substrates for Ugi reaction resulting in a formation of tripeptide skeletons. Further functionalization of the obtained products led to a synthesis of tripeptide aldehydes. All stereoisomers of MG-132 were synthesized and studied as potential inhibitors of chymotrypsin-like, trypsin-like, and peptidylglutamyl peptide hydrolyzing activities of proteasome. These studies demonstrated the influence of absolute configuration of chiral aldehydes on the cytostatic/cytotoxic effects of the synthesized compounds and revealed that only (S,R,S)-(-)-2 stereoisomer is a more potent proteasome inhibitor than MG-132.
In this work, complexes of Zr(IV) and Al(III) cations with tert-butyl substituted tetraphenylporphyrin or tetraazaporphine were tested as F À -selective ionophores in plasticized aminated or carboxylated PVC membranes of ion-selective electrodes. It was found that functional groups present in the backbone of applied polymers influence the complexing properties of tested ligands, causing changes of F À -selectivity of electrodes prepared with their use in comparison with the electrodes with unmodified PVC membranes. This work shows, that application of functionalized PVC can eliminate the need of relatively expensive ionic sites addition to ion-selective membranes doped with metallocomplexes.
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