Fluorinated Triazole Foldamers: Folded or Extended Conformational Preferences.

The Ministère de l'Enseignement Supérieur et de la Recherche (MESR) is thanked for financial support for José Laxio Arenas. The China Scholarship Council is thanked for financial support for Yaochun Xu. The authors thank Pr.

Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells.

A lead compound with the (1,3,4-thiadiazol-2-yl)-acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities.

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands.

Pentapeptides having the sequence R-HN-Ala-Val--Val-Leu-OMe, where the central residue is L-serine, L-threonine, (2,3)-L-CF-threonine and (2,3)-L-CF-threonine were prepared. The capacity of (2,3)- and (2,3)-CF-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular dynamics simulations. CF-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues.

Characterization of the stereochemical structures of 2H-thiazolo[3,2-a]pyrimidine compounds and their binding affinities for anti-apoptotic Bcl-2 family proteins.

In a previous study we reported a class of compounds with a 2H-thiazolo[3,2-a]pyrimidine core structure as general inhibitors of anti-apoptotic Bcl-2 family proteins. However, the absolute stereochemical configuration of one carbon atom on the core structure remained unsolved, and its potential impact on the binding affinities of compounds in this class was unknown. In this study, we obtained pure R and S enantiomers of four selected compounds by HPLC separation and chiral synthesis.

Discovery and development of thiazolo[3,2-a]pyrimidinone derivatives as general inhibitors of Bcl-2 family proteins.

A class of compounds with a common thiazolo[3,2-a]pyrimidinone motif has been developed as general inhibitors of Bcl-2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization-based competitive binding assay. Its binding to the Bcl-x(L) protein was further confirmed by (15) N-HSQC NMR experiments.