Search

An optically active polythiophene, which can fold into a one-handed helical conformation under good solvent conditions, has been developed., We report an optically active polythiophene capable of forming a one-handed helically folded conformation without needing aggregate formation, poor solvent conditions, hydrogen-bonded ion-pair formation or guest addition. The target polythiophene (poly-TR) with a static axial chirality in the main chain was synthesized via Stille coupling copolymerization of a glucose-linked chiral 5,5′-dibromobithiophene with 2,5-bis(stannyl)thiophene. Poly-TR showed a characteristic circular dichroism and circularly polarized luminescence, which were completely different to those observed for an analogous polymer (poly-PhR) and the corresponding unimer/dimer model compounds. This chiroptical study, combined with the results of all-atom molecular dynamics simulations, revealed that poly-TR can fold into a left-handed helical conformation under good solvent conditions. Partial conformational regulation derived from the fixed syn-conformation of the chiral bithiophene unit was considered a key factor in producing the one-handed helical polythiophene.

We have designed and synthesized new types of pyrrole (P)-imidazole (I) polyamide conjugates 1 and 2 possessing a suberoylanilide hydroxamic acid (SAHA) moiety that is a strong inhibitor of histone deacetylase (HDAC). SAHA conjugate 2 was designed to target the promoter region of the p16 tumor suppressor gene. The DNA binding affinity of SAHA conjugate 2 to its target sequence was examined using surface plasmon resonance. HDAC inhibition activity of conjugates 1 and 2 was evaluated using a colorimetric assay. The results demonstrated that even though it possesses the relatively large SAHA moiety, conjugate 2 has high DNA sequence-specific binding properties and moderate HDAC inhibitory activity in vitro. SAHA conjugate 2 was found to cause morphological changes in HeLa cells and to induce selective Histone H3 lysine 9 acetylation.

The catalytic polypeptide of DNA-dependent protein kinase (p470) is encoded by the gene responsible for murine severe combined immunodeficiency (SCID) devoid of DNA double-strand break repair and V(D)J recombination. Here, we have characterized the role of p470 in cell proliferation using SCID mice and the cell lines. In accord with DNA histogram patterns, SCID cell lines (SD/SD-eA and SC3VA2) expressing extremely low level of DNA-PK activity grew faster than a normal mouse cell line (CB/CB-eB) and SC3VA2 complemented with human p470 gene (RD13B2). In regenerating liver after partial hepatectomy, de novo DNA synthesis determined by [(3)H]thymidine incorporation started at 30h in C.B-17/Icr-SCID (SCID) mice and at around 36h in C.B-17/Icr (C.B-17) mice. Compared with normal cells, SCID cells contained slightly higher levels of transcripts of cyclin A, cyclin E, B-Myb and dihydrofolate reductase, which are regulated by E2F-1. E2F-1 playing a key role in G1- to S-phase progression was phosphorylated in vitro by DNA-PK. Importantly, the E2F-1 promoter transcriptional activity in SCID cell lines (SD/SD-eA and SC3VA2) was 4-5-fold higher than that in CB/CB-eB and RD13B2. These results suggest that p470 is involved in down-regulation of cell cycle progression through E2F-1-responsible genes.