Tat, an essential human immumodeficiency virus type 1 protein interact s with the t ransactivation response element (TAR) and stimulates transcription from the viral long-terminal repeat (LTR). Blockage of Tat-TAR interaction halt sviral transcription and hence replication. In recent years a numbe of studies have suggested various chemicals and/or genetic inhibitors targeting TAR RNA for inhibition of Tatactivated t ranscription. Here, we report these research works.

Abstract To study the interactions of these compounds with calf thymus DNA(CT-DNA), seven b-carboline-3-carboxamides were designed and synthesized. The interactions of these compounds with CT-DNA were determined by the viscometric titration assay and Tm (melting temperature) value assay. Binding strengths were evaluated by spectrophotometric titration experiment and microcalorimetric measurement. The interactions of these compounds were tested with CT-DNA. It was showed that all of these compounds were able to change the Tm value of CT-DNA. The results of viscometric titration assay indicated that these compounds interacted with CT-DNA by intercalation. Spectrophotometric titration experiment showed that the binding strengths of these compounds with CT-DNA were different, which was well in agreement with the cell culture results. The binding was driven by entropy according to the results of the microcalorimetric measurement. This series of b-carboline-3-carboxamides is DNA targeting compounds. Their obvious antitumor biological effect is based on the intercalation with DNA base-pairs.

The complex [Mn(L)(NO) (HO)] (1) (L52H-5-hydroxy-1, 2, 5-oxadiazo[3, 4-f]1,10-phenanthroline) was synthesized and character-3222 ized by elemental analysis, IR and UV. The crystal and molecular structure of 1 was determined by single-crystal X-ray diffraction; crystal data: light yellow, monoclinic, space group P2/n, Z54, a 57.432 (2) A, b59.582(3) A, c 523.445(7) A, b 590.519 (5)8. The Mn atom in 11 is hexa-coordinated in a distorted octahedral arrangement by two N atoms of the ligand L and four O atoms of two water molecules and two nitrate anions. Biological tests in vitro showed that 1 has significant antitumor activity against HL-60, KB, Hela and BGC-823 cells. The interaction of 1 with calf thymus DNA was investigated by absorption titration, thermal denaturation and viscosity measurements. The results suggest that 1 binds with DNA by intercalating via the ligand L.

Synthesis of unimolecularly circular G-quadruplex has been accomplished for the first time during our investigation on the template basis of G-quadruplex through chemical ligations of guanine-rich linear sequencesofoligodeoxyribonucleotides. Theuniqueness of this newly designed circularization course is its self-recognition and self-templating on the scale of individual strand of zligodeoxyribonucleotide in which the same linear sequence serves both as a template and as a substrate simultaneously. The results from our exonuclease and DNAse hydrolysis studies confirm that there is indeed absence of open termini within the structure of the identified circular product. Our subsequent investigation on the loopsize effect indicates that the unimolecularly circular G-uadruplex possessing two or more thymine nucleotides within their connecting loops is readily attainable, while the linear sequence with a single thymine nucleotide between guanine tracts is not a proper precursor for our ligation reaction. In addition, conformation dependency of the circularization course as well as the effects of alkali ions, pH values and concentration of potassium ions on the circularization reaction are examined during our investigation. The implication of our current studies and possible application of the obtained unimolecularly circular G-quadruplex in certain biological processes are also discussed in this report.

Replication of HIV-1 requires specific interactions of Tat protein with TAR RNA. Disruption of Tat-TAR RNA interaction could inhibit HIV-1 replication. Here four target compounds were designed and synthesized to bind to TAR RNA for blocking the interaction of Tat-TAR RNA. The core molecule 6,60-diamino-6,60-dideoxy-a,a-trehalose was obtained from selective bromination of, a,a-trehalose at C-6,60, followed by acetylation, azide displacement, deacetylation, and reduction. Coupling of the core molecule with the protected amino acid, then deprotection and guanidinylation generated the novel a,a-trehalose derivatives. Their abilities to inhibit Tat-TAR RNA interaction in human cells were determined by a Tat-dependent HIV-1 LTR-driven CAT assays.