(A). Regulation of B-/Z-DNA transition in modified oligonucleotides; (B). Synthesis of cationic BODIPY analogues for antimicrobial and anticancer applications

Abstract

A. In this work, LNA-dG was incorporated into d(CG)6 sequence in a site-specific manner through the phosphoramidite chemistry-based solid phase synthesis to investigate the impact of this modification on the B→Z-DNA transition. Circular dichroism study showed that the incorporation of a single LNA-dG unit into d(CG)6 at internal positions virtually suppressed Z-DNA formation at 4 M NaCl concentration, whereas the presence of single LNA-dG unit towards the terminal ends showed only partially inhibition of B→Z-DNA transition. To further understand the influence of chemical modification on B→Z-DNA transition, modification at C8-position on LNA-dG residue was explored. Towards this goal, compounds such as 8-bromo-5′-dimethoxytrityl-N-dimethylformamidine-(2′-O,4′-C-methylene)-guanosine-3′-O-(2-cyanoethyl)-N,N-diisopropy phosphoramidite and 8-bromo-2′-deoxy-5′-O-dimethoxy-N-[(dimethylamino)methylene]-2′-fluoroguanosine-3′-O-(2-cyanoethyl)-N,N-diisopropyl phosphoramidite were synthesized. B. In this study, N,N,N-trimethyl-2-(4,4-difluoro-2,6-diiodo-4-bora-3a,4a-diaza-s-indacen-8-yl) ethylammonium iodide 111 was successfully synthesized. Singlet oxygen generation experiments suggested that BODIPY 111 is ~2.5 times more efficient with respect to Rose Bengal (RB) in generating singlet oxygen. However, based on the cell-culture experiment, BODIPY 111 treated culture plates showed only slight reduction in CFUs compared to Rose Bengal and control plates. BODIPY compounds 107 (iodinated-fluoro-BODIPY), 130 (brominated-fluoro-BODIPY) and 110 (brominated-meso-dimethylamine-fluoro-BODIPY) showed excellent stability both in dark and in light conditions and were found to be very efficient in generating singlet oxygen when compared to RB.