Tianhu Li

Ultrasensitive and Selective Colorimetric DNA Detection by Nicking Endonuclease Assisted Nanoparticle Amplification

The ability to sense and detect ultralow concentrations of specific DNA sequences by using simple and inexpensive assays is important in clinical diagnostics, mutation detection, and biodefense applications. Conventional methods that use radioactive [P]-labeled nucleic acid probes or the polymerase chain reaction (PCR) coupled with molecular fluorophore assays offer high sensitivity of detection, but they suffer from several drawbacks that include complex handling procedures, easy contamination, high cost, and lack of portability. In contrast, metal-nanoparticle-based homogeneous colorimetric detection of oligonucleotides holds great promise for low-cost, low-volume, and rapid readout of a target DNA sequence. Despite these attractions, a number of notable challenges associated with this detection system still exist, such as relatively low sensitivity (ca. 10 nm) and the need for stringent control over melting temperatures for the detection of a single-base mismatch in DNA. In addition, this system is generally limited to the detection of short singlestranded oligonucleotides. Herein, we describe homogeneous colorimetric DNA detection by a novel nicking endonucleaseassisted nanoparticle amplification (NEANA) process that is capable of recognizing long single-stranded oligonucleotides with single-base mismatch selectivity and a 10-fold improvement in amplification (ca. 10 pm). A three-component sandwich assay format that includes a target DNA and two sets of oligonucleotide-modified nanoparticle probes is typically used in conventional homogenous nanoparticle-based colorimetric DNA detection. The target DNA also serves as a linker strand that triggers particle aggregation and a concomitant color change. Thus, the colorimetric detection limit is directly associated with the minimum number of the linkers required to initiate particle aggregation that can be visualized with the naked eye. At low linker concentrations (ca. 10 nm), aggregation of 14 nm nanoparticles does not exhibit sharp colorimetric melting transitions (see the Supporting Information). Larger particle probes and reduced oligonucleotide surface coverages can improve assay sensitivities, but sedimentation becomes more dominant with increase in the particle size. To increase the sensitivity of homogeneous nanoparticlebased assays, we have developed a detection system that contains an additional oligonucleotide strand as the linker, and a nicking endonuclease (NEase; Figure 1). Unlike

Ultrasensitive Colorimetric DNA Detection using a Combination of Rolling Circle Amplification and Nicking Endonuclease‐Assisted Nanoparticle Amplification (NEANA)

A combination of rolling circle amplification and nicking endonuclease-assisted nanoparticle amplification (NEANA) is used for the rapid, colorimetric detection of DNA. The integration of rolling circle amplification into the NEANA approach allows for detection of oligonucleotides with arbitrary sequences at ultralow concentrations.

Synthesis and biological properties of C12,13-cyclopropylepothilone A and related epothilones

BACKGROUND The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority. RESULTS The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified. CONCLUSIONS The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.

Inhibition of topoisomerase I by naphthoquinone derivatives

Alkannin and shikonin are naturally occurring naphthoquinones. We have tested several derivatives of the title compounds and we have found that naphthoquinones bearing at least one phenolic hydroxyl group are potent inhibitors of topoisomerase I. The ability of the tested compounds to complex Zn++ parallels with a few exceptions their topoisomerase I inhibition properties while their intercalation and redox properties do not.

Colorimetric Detection of HIV-1 Ribonuclease H Activity by Gold Nanoparticles

Scheme 1 . Illustration of colorimetric detection of HIV-1 RNase H activity using unmodifi ed gold nanoparticles. Acquired immune defi ciency syndrome (AIDS) is generally characterized by infection of human immunodefi ciency virus type 1 (HIV-1). Despite enormous efforts in developing antiretroviral drugs, coping with the drug resistance of HIV-1 remains a daunting task. [ 1 ] The ribonuclease H (RNase H) activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the viral replication cycle and degrades the RNA strand of an RNA–DNA hybrid. [ 2 ]

Synthesis and Biological Activity of Sarcodictyins

A new class of potential antitumor agents with a taxol-like mechanism of action is presented by the sarcodictyins 1. Modification of the reported syntheses of sarcodictyins permitted the preparation of additional derivatives, the biological properties of which are highly dependent upon the structure.

EcoRI-Modified Gold Nanoparticles for Dual-Mode Colorimetric Detection of Magnesium and Pyrophosphate Ions

Magnesium in its ionic form (Mg 2 + ) is essential for many physiological processes, including much of metabolism, enzyme activation and catalysis, photosynthesis development, signal transduction, and protection against hypertension and blood vessel spasm. [ 1 ] Therefore, it has been long recognized that for suitable diagnosis of various ailments, the accurate and rapid measurement of Mg 2 + is important. Additionally, the ability to detect Mg 2 + is also important in the area of environmental monitoring for effective pollution control. [ 2 ]

Synthesis of 5-(7-hydroxyhept-3-enyl)-1,2-dithiolan-3-one 1-oxide, a core functionality of antibiotic leinamycin

5-(7-Hydroxyhept-3-enyl)-1,2-dithiolan-3-one 1-oxide 1 possessing both the 1,2-dithiolan-3-one 1-oxide five-membered ring and the double bond at the gamma position of the heterocycle, characteristic of the antibiotic leinamycin, was synthesized. In addition, the activated ester form of 1 was prepared that may be useful for coupling 1 to certain DNA-binding agents.

Totalsynthese von Epothilon E und seitenkettenmodifizierten Epothilon-Analoga durch Stille-Kupplung

Ringschlus durch Olefinmetathese (siehe unten, a), Abspaltung der Schutzgruppe (b), Stille-Kupplung (c) und die abschliesende Epoxidierung (d) sind die wesentlichen Schritte der ersten Totalsynthese des naturlich vorkommenden Epothilons E 1. Ausgehend von dem Produkt der Olefinmetathese, einer sehr fortgeschrittenen Zwischenstufe, ist eine Fulle von Epothilon-E-Analoga mit unterschiedlichen aromatischen Resten in der Seitenkette zuganglich. TBS = tBuMe2Si.

Total synthesis of 26-hydroxyepothilone B and related analogues

A series of 26-substituted epothilones B (3, 22, 23a–n and 24a–h,j–l,o) have been constructed by total synthesis involving a selective Wittig olefination, an aldol reaction and a macrolactonization as key steps.