Upregulation of p53 through induction of MDM2 degradation: Anthraquinone analogs.

In a previous study, a novel anthraquinone analog BW-AQ-101 was identified as a potent inducer of MDM2 degradation, leading to upregulation of p53 and apoptosis in cell culture studies. In animal models of acute lymphocytic leukemia, treatment with BW-AQ-101 led to complete disease remission. In this study, we systematically investigated the effect of substitution patterns of the core anthraquinone scaffold.

Biphasic actions of SecA inhibitors on Prl/Sec suppressors: Possible physiological roles of SecA-only channels.

SecA is an essential component in the bacterial Sec-dependent protein translocation process. We previously showed that in addition to the ubiquitous, high-affinity SecYEG-SecDF·YajC protein translocation channel, there is a low-affinity SecA-only channel that elicits ion channel activity and promotes protein translocation. The SecA-only channels are less efficient, and like Prl suppressors, lack signal peptide specificity; they function in the absence of signal peptides.

Using Chemical Probes to Assess the Feasibility of Targeting SecA for Developing Antimicrobial Agents against Gram-Negative Bacteria.

With the widespread emergence of drug resistance, there is an urgent need to search for new antimicrobials, especially those against Gram-negative bacteria. Along this line, the identification of viable targets is a critical first step. The protein translocase SecA is commonly believed to be an excellent target for the development of broad-spectrum antimicrobials.

A metal-free turn-on fluorescent probe for the fast and sensitive detection of inorganic azides.

Sodium azide is toxic and widely used in agricultural, commercial products, and research laboratories. Thus it is of a significant environmental concern and there is a need for the development of a rapid detection method. A fluorogenic dibenzylcyclooctyne derivative (Fl-DIBO) is herein described as a fluorescent probe for the rapid detection of inorganic azide via Strain-Promoted Azide-Alkyne Cycloaddition (SPAAC).

Design, Synthesis and Evaluation of Triazole-Pyrimidine Analogues as SecA Inhibitors.

SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. Through a combination of virtual screening and experimental exploration of the surrounding chemical space, we identified a hit bistriazole SecA inhibitor, SCA-21, and studied a series of analogues by systematic dissections of the core scaffold. Evaluation of these analogues allowed us to establish an initial structure-activity relationship in SecA inhibition.

Click with a boronic acid handle: a neighboring group-assisted click reaction that allows ready secondary functionalization.

The feasibility of a neighboring boronic acid-facilitated facile condensation of an aldehyde is described. This reaction is bio-orthogonal, complete at room temperature within minutes, and suitable for bioconjugation chemistry. The boronic acid group serves the dual purpose of catalyzing the condensation reaction and being a handle for secondary functionalization.

Post-synthesis DNA modifications using a trans-cyclooctene click handle.

Post-synthesis DNA modification is a very useful method for DNA functionalization. This is achieved by using a modified NTP, which has a handle for further modifications, replacing the corresponding natural NTP in polymerase-catalyzed DNA synthesis. Subsequently, the handle can be used for further functionalization after PCR, preferably through a very fast reaction.

A click-and-release approach to CO prodrugs.

Carbon monoxide belongs to the family of signaling molecules and has been shown to possess therapeutic effects. Similar to NO, safe delivery of CO is a key issue in developing CO-based therapeutics. Herein we report a "click and release" CO-prodrug approach, which allows the release of CO under physiological conditions without the need for light irradiation.

Redox-based selective fluorometric detection of homocysteine.

Plasma homocysteine (Hcy) is an important risk factor for various diseases. A novel redox-sensitive fluorescent probe is developed for the selective detection of Hcy. A linear calibration curve has been obtained in buffer and plasma for the quantitative determination of Hcy in such media.

3,6-Substituted-1,2,4,5-tetrazines: tuning reaction rates for staged labeling applications.

Cycloaddition reactions involving tetrazines have proven to be powerful bioorthogonal tools for various applications. Conceivably, sequential and selective labeling using tetrazine-based reactions can be achieved by tuning the reaction rate. By varying the substituents on tetrazines, cycloaddition rate variations of over 200 fold have been achieved with the same dienophile.

2,6-dansyl azide as a fluorescent probe for hydrogen sulfide.

A second-generation sulfonyl azide-based fluorescent probe, 2,6-DNS-Az, has been developed for the quantitative detection of H2S in aqueous media such as phosphate buffer and bovine serum. Compare to the first-generation 1,5-DNS-Az probe, this probe shows both high sensitivity in phosphate buffer without the need for addition of surfactant and selectivity for sulfide over other anions and biomolecules, and thus can be used as a useful tool for detection of H2S in the biological system.

An unexpected copper catalyzed 'reduction' of an arylazide to amine through the formation of a nitrene intermediate.

Azido nitrobenzoxadiazole (NBD) was observed to undergo a 'reduction' reaction in the absence of an obvious reducing agent, leading to amine formation. In the presence of an excess amount of DMSO, a sulfoxide conjugate was also formed. The ratio of these two products was both temperature- and solvent-dependent, with the addition of water significantly enhancing the ratio of the 'reduction' product.

Arylboronic acid chemistry under electrospray conditions.

Boronic acids are important in the organic and biological arenas. Thus, their identification and characterization are important. ESI-MS is a well-known tool for such uses.

Rapid and specific post-synthesis modification of DNA through a biocompatible condensation of 1,2-aminothiols with 2-cyanobenzothiazole.

Post-synthesis modification of DNA is an important way of functionalizing DNA molecules. Herein, we describe a method that first enzymatically incorporates a cyanobenzothiazole (CBT)-modified thymidine. The side-chain handle CBT can undergo a rapid and site-specific cyclization reaction with 1,2-aminothiols to afford DNA functionalization in aqueous solution.

A Novel Base-Promoted Cyclization: Synthesis of Substituted Benzo[b]furans.

A new base-promoted cyclization for the synthesis of substituted benzo[b]furans is described. This method is simple and inexpensive and gives good yields.

A fluorescent probe for rapid aqueous fluoride detection and cell imaging.

A stable and highly selective fluorescent probe has been designed and synthesized for the rapid detection of fluoride ions (F(-)) in aqueous solution and living cells. The design was based on the high reactivity of F(-) toward a silyl group.

Clicking 1,2,4,5-tetrazine and cyclooctynes with tunable reaction rates.

Substituted tetrazines have been found to undergo facile inverse electron demand Diels-Alder reactions with "tunable" reaction rates.

Design, synthesis, and polymerase-catalyzed incorporation of click-modified boronic acid-TTP analogues.

DNA molecules are known to be important materials in sensing, aptamer selection, nanocomputing, and construction of unique architectures. The incorporation of modified nucleobases affords unique DNA properties for applications in areas that would otherwise be difficult or not possible. Earlier, we demonstrated that the boronic acid moiety can be introduced into DNA through polymerase-catalyzed reactions.

Using boronolectin in MALDI-MS imaging for the histological analysis of cancer tissue expressing the sialyl Lewis X antigen.

Certain carbohydrate-based biomarkers are known to correlate with cancer formation and progression. By targeting sialyl Lewis X, we have developed the first boronolectin-MS tag conjugate, which allows for MALDI-based imaging of cancer based on its cell surface carbohydrate.

Facile derivatization of azide ions using click chemistry for their sensitive detection with LC-MS.

By employing a click reaction, a novel method was developed for the sensitive detection of inorganic azides at as low as 21 ppb.

The first chemical synthesis of boronic acid-modified DNA through a copper-free click reaction.

The first chemical incorporation of the boronic acid group into DNA using a copper-free click reagent was reported. Compared with the PCR-based method, this approach allows for site-specific incorporation and synthesis on a larger scale.

Click reactions and boronic acids: applications, issues, and potential solutions.

Boronic acids have been widely used in a wide range of organic reactions, in the preparation of sensors for carbohydrates, and as potential pharmaceutical agents. With the growing importance of click reactions, inevitably they are also applied to the synthesis of compounds containing the boronic acid moiety. However, such applications have unique problems.

Boronic acid-modified DNA that changes fluorescent properties upon carbohydrate binding.

A long wavelength boronic acid-modified TTP (NB-TTP) has been synthesized and enzymatically incorporated into DNA. Such DNA shows intrinsic fluorescent changes upon carbohydrate addition.

Fluoride protects boronic acids in the copper(I)-mediated click reaction.

Fluoride has been found to protect boronic acids from copper(i)-mediated decomposition; such findings should be very useful for the preparation of boronic acid-based carbohydrate sensors and boronic acid conjugates using the copper(i)-mediated click reaction.