蛋白酶体是一种庞大的、多价复合酶，它在承担细胞内蛋白质降解的泛蛋白-蛋白酶体通路（UPP）的关键步骤中起催化作用。UPP不仅可以催化降解异常蛋白质，而且在许多调控蛋白质的更新和加工过程中起重要作用，这些蛋白质的催化过程涉及到人类疾病发病机制的重要生化机制。目前，与UPP有关的酶已被认为是药物设计的分子靶位，蛋白酶体参与调节多种细胞功能，其特异性抑制剂不仅可以作为研究UPP的有利工具，而且也是潜在的抗肿瘤、抗炎药物。本文综述了蛋白酶体抑制剂的药理活性研究进展。

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.

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.

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.

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.