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1.
ACS Cent Sci ; 2(1): 27-31, 2016 Jan 27.
Article in English | MEDLINE | ID: mdl-27163023

ABSTRACT

The fungal-derived Taiwanese natural product antroquinonol A has attracted both academic and commercial interest due to its reported exciting biological properties. This reduced quinone is currently in phase II trials (USA and Taiwan) for the treatment of non-small-cell lung carcinoma (NSCLC) and was recently granted orphan drug status by the FDA for the treatment of pancreatic cancer and acute myeloid leukemia. Pending successful completion of human clinical trials, antroquinonol is expected to be commercialized under the trade name Hocena. A synthesis-enabled biological re-examination of this promising natural product, however, reveals minimal in vitro and in vivo antitumor activity in preclinical models.

2.
J Am Chem Soc ; 136(14): 5279-82, 2014 Apr 09.
Article in English | MEDLINE | ID: mdl-24654983

ABSTRACT

A simple method for direct C-H imidation is reported using a new perester-based self-immolating reagent and a base-metal catalyst. The succinimide products obtained can be easily deprotected in situ (if desired) to reveal the corresponding anilines directly. The scope of the reaction is broad, the conditions are extremely mild, and the reaction is tolerant of oxidizable and acid-labile functionality, multiple heteroatoms, and aryl iodides. Mechanistic studies indicate that ferrocene (Cp2Fe) plays the role of an electron shuttle in the decomposition of the perester reagent, delivering a succinimidyl radical ready to add to an aromatic system.


Subject(s)
Benzene Derivatives/chemistry , Ferrous Compounds/chemistry , Heterocyclic Compounds/chemistry , Imides/chemical synthesis , Catalysis , Imides/chemistry , Metallocenes , Molecular Structure
3.
Org Biomol Chem ; 11(31): 5074-8, 2013 Aug 21.
Article in English | MEDLINE | ID: mdl-23824077

ABSTRACT

Signal amplification methods are of obvious importance for various diagnostic assays. We have developed a new small-molecule-based probe that, upon activation with sub-stoichiometric amounts of hydrogen peroxide, produces an auto-inductive amplification reaction. The signal is produced through the oxidation reaction of hydroquinone to the corresponding quinone derivative by molecular oxygen. This oxidation is accompanied by the formation of hydrogen peroxide, which can enter the amplification sequence and initiate a new diagnostic cycle. The generated quinone is composed of a donor-acceptor conjugated pair and fluoresces at a distinct wavelength, allowing the formation to be monitored by a convenient fluorescence assay.

4.
Org Biomol Chem ; 11(17): 2903-10, 2013 May 07.
Article in English | MEDLINE | ID: mdl-23519143

ABSTRACT

Bacteria will gain an advantage if they are able to metabolize nutrients that are inaccessible for other bacteria. To demonstrate this principle, we developed a simple model system, which mimics how bacteria exploit natural carbon sources. A masked glucose precursor that is activated by ß-galactosidase was used as a carbon source for bacterial growth in a glucose-deficient medium. No bacterial growth was observed in the presence of control substances in which ß-galactosidase mediated cleavage did not lead to glucose release. This study represents a proof-of-principle example in which a bacterium can grow in a nutrient-free medium by inducible, enzyme-mediated nutrient release from a precursor.


Subject(s)
Escherichia coli/growth & development , Glucose/metabolism , beta-Galactosidase/metabolism , Escherichia coli/chemistry , Escherichia coli/enzymology , Glucose/chemistry , beta-Galactosidase/chemistry
6.
Org Biomol Chem ; 10(4): 710-5, 2012 Jan 28.
Article in English | MEDLINE | ID: mdl-22159494

ABSTRACT

In recent years, there has been a massive effort to develop molecular probes with optical modes of action. Probes generally produce detectable signals based on changes in fluorescence properties. Here, we demonstrate the potential of self-immolative molecular adaptors as a platform for Turn-On probes based on the FRET technique. The probe is equipped with identical fluorophore pairs or a fluorophore/quencher FRET pair and a triggering substrate. Upon reaction of the analyte of interest with the triggering substrate, the self-immolative adaptor spontaneously releases the two dye molecules to break off the FRET effect. As a result, a new measurable fluorescent signal is generated. The fluorescence obtained can be used to quantify the analyte. The modular structure of the probe design will allow the preparation of various chemical probes based on the FRET activation technique.


Subject(s)
Fluorescence Resonance Energy Transfer/methods , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/metabolism , Hydrogen Peroxide/metabolism
7.
Chemistry ; 17(43): 12123-8, 2011 Oct 17.
Article in English | MEDLINE | ID: mdl-21905139

ABSTRACT

A new example of an exponential signal amplification strategy for the direct detection of fluoride is demonstrated. The amplification occurred through reaction of fluoride with a responsive chromogenic probe. The probe activity is based on a unique dendritic chain reaction that generates a fluoride anion, which is the analyte of interest, during the disassembly pathway of the dendritic probe. This autoinductive amplification mechanism may be applied for detection of other analytes by coupling activity of a modified probe with that of the fluoride amplifier.


Subject(s)
Chromogenic Compounds/analysis , Chromogenic Compounds/chemistry , Coloring Agents/chemistry , Dendrimers/analysis , Dendrimers/classification , Fluorides/analysis , Fluorides/chemistry , Nucleic Acid Amplification Techniques/methods , Biotechnology , Catalysis , Molecular Probe Techniques , Molecular Structure
8.
Chem Commun (Camb) ; 46(35): 6575-7, 2010 Sep 21.
Article in English | MEDLINE | ID: mdl-20714571

ABSTRACT

A new dendritic chain reaction probe system was demonstrated to produce exponential signal amplification for the detection of sulfhydryl compounds.


Subject(s)
Sulfhydryl Compounds/chemistry , Amidohydrolases/metabolism , Nitrobenzoates/chemistry , Spectrophotometry
9.
J Am Chem Soc ; 132(11): 3945-52, 2010 Mar 24.
Article in English | MEDLINE | ID: mdl-20192194

ABSTRACT

New analytical diagnostic techniques that are based on signal-amplification mechanisms could significantly improve the sensitivity of detection of various analytes. We have developed a new approach to achieving exponential amplification of a diagnostic signal through a two-component dendritic chain reaction. The chain reaction generated the analyte of interest and thereby initiated additional diagnostic cycles. The system was designed for the detection of hydrogen peroxide and produced significantly larger intensity of diagnostic signal than a classic probe. In addition, a mathematical model that simulates the disassembly kinetics of one-component and two-component reactions was developed and shown to correlate well with the observed experimental data. The modularity and flexibility of a two-component detection system should allow extension to the detection of other analytes.

10.
J Am Chem Soc ; 131(29): 9934-6, 2009 Jul 29.
Article in English | MEDLINE | ID: mdl-19569684

ABSTRACT

Signal amplification techniques are broadly used to improve the detection sensitivity of various analytes for diagnostic purposes. We have developed a novel, non-PCR-based modular technique for exponential amplification of diagnostic signals that is conveniently performed in an aqueous environment. The technique is based on a distinctive dendritic chain reaction (DCR); the diagnostic signal is generated upon disassembly of a self-immolative dendrimer that releases chromogenic molecules. Under ideal conditions, a single analyte molecule initiates a DCR that generates a strong diagnostic signal. When coupled with a protease diagnostic probe, the DCR technique detected the activity of penicillin-G-amidase with high sensitivity. This is the first example of exponential signal amplification performed under aqueous conditions that is not based on PCR.


Subject(s)
Chemistry Techniques, Analytical/methods , Dendrimers/analysis , Dendrimers/chemical synthesis , Amidohydrolases/analysis , Amidohydrolases/metabolism , Dendrimers/chemistry , Diagnostic Tests, Routine/methods , Hydrogen Peroxide/chemistry , Molecular Probes/analysis , Molecular Probes/chemistry , Penicillin G/analysis , Penicillin G/metabolism , Sensitivity and Specificity
11.
Chem Commun (Camb) ; (44): 5701-3, 2008 Nov 30.
Article in English | MEDLINE | ID: mdl-19009053

ABSTRACT

A new self-immolative dendritic probe directly detects triacetone triperoxide through amplification of a single cleavage event initiated by one molecule of hydrogen peroxide into multiple-release of fluorogenic end-groups.

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