A5030863493- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Advanced biosensing and bioanalysis techniques
- Pharmacological Receptor Mechanisms and Effects
- Quantum Dots Synthesis And Properties
- Neuroscience and Neuropharmacology Research
- Chemical synthesis and alkaloids
- Alkaloids: synthesis and pharmacology
- Asymmetric Synthesis and Catalysis
- Neurotransmitter Receptor Influence on Behavior
- Synthesis and Biological Evaluation
- Synthetic Organic Chemistry Methods
- Metal complexes synthesis and properties
- Molecular Junctions and Nanostructures
- Mass Spectrometry Techniques and Applications
- Crystal structures of chemical compounds
- Analytical Chemistry and Chromatography
- Analytical Chemistry and Sensors
- HIV/AIDS drug development and treatment
- Energetic Materials and Combustion
- Synthesis and Catalytic Reactions
United States Naval Research Laboratory
2013-2022
Massachusetts Institute of Technology
2021
Naval Research Laboratory Center for Bio/Molecular Science and Engineering
2008-2017
United States Navy
2015-2017
University of Wisconsin–Milwaukee
2003-2016
National Institute on Alcohol Abuse and Alcoholism
2008-2015
University of Maryland, Baltimore
2003-2015
National Institutes of Health
2004-2015
Center for Information Technology
2007-2015
K Lab (United States)
2009-2013
A successful structure-based design of a class non-peptide small-molecule MDM2 inhibitors targeting the p53-MDM2 protein-protein interaction is reported. The most potent compound 1d binds to protein with Ki value 86 nM and 18 times more than natural p53 peptide (residues 16-27). Compound in inhibition cell growth LNCaP prostate cancer cells wild-type shows only weak activity PC-3 deleted p53. Importantly, has minimal toxicity normal epithelial cells. Our studies provide convincing example...
We demonstrate the use of luminescent QDs conjugated to antibody fragments develop solution-phase nanoscale sensing assemblies, based on fluorescence resonance energy transfer (FRET) for specific detection explosive 2,4,6-trinitrotoluene (TNT) in aqueous environments. The hybrid sensor consists anti-TNT attached a hydrophilic QD via metal-affinity coordination. A dye-labeled TNT analogue prebound binding site quenches photoluminescence proximity-induced FRET. Analysis data collected at...
Dopamine, serotonin, and norepinephrine are essential for neurotransmission in the mammalian system. These three neurotransmitters have been focus of considerable research because modulation their production interaction at monoamine receptors has profound effects upon a multitude pharmacological outcomes. Our interest focused on neurotransmitter reuptake mechanisms search medications cocaine abuse. Herein we describe synthesis biological evaluation an array 2-aminopentanophenones. This...
We demonstrate the use of a hybrid fluorescent protein semiconductor quantum dot (QD) sensor capable specifically monitoring caspase 3 proteolytic activity. mCherry monomeric red engineered to express an N-terminal cleavage site was ratiometrically self-assembled surface QDs using metal-affinity coordination. The proximity QD allows it function as efficient fluorescence resonance energy transfer acceptor. Addition enzyme QD−mCherry conjugates cleaved linker sequence, altering with and...
Small-molecule inhibitors that block the MDM2-p53 protein–protein interaction (MDM2 inhibitors) are being intensely pursued as a new therapeutic strategy for cancer treatment. We previously published series of spirooxindole-containing compounds class MDM2 small-molecule inhibitors. report herein reversible ring-opening-cyclization reaction some these spirooxindoles, which affords four diastereomers from single compound. Our biochemical binding data showed stereochemistry in this has major...
The first generation of luminescent semiconductor quantum dot (QD)-based hybrid inorganic biomaterials and sensors is now being developed. It crucial to understand how bioreceptors, especially proteins, interact with these nanomaterials. As a model system for study, we use Rhodamine red-labeled engineered variants Escherichia coli maltose-binding protein (MBP) coordinated the surface 555-nm emitting CdSe-ZnS core–shell QDs. Fluorescence resonance energy transfer studies were performed...
The unique properties provided by hybrid semiconductor quantum dot (QD) bioconjugates continue to stimulate interest for many applications ranging from biosensing energy harvesting. Understanding both the structure and function of these composite materials is an important component in their development. Here, we compare architecture that results using two common self-assembly chemistries attach DNA QDs. modified display either a terminal biotin or oligohistidine peptidyl sequence was...
Cell penetrating peptides facilitate efficient intracellular uptake of diverse materials ranging from small contrast agents to larger proteins and nanoparticles. However, a significant impediment remains in the subsequent compartmentalization/endosomal sequestration most these cargoes. Previous functional screening suggested that modular peptide originally designed deliver palmitoyl-protein thioesterase inhibitors neurons could mediate endosomal escape cultured cells. Here, we detail...
Recent studies show that polyvalent, ligand-modified nanoparticles provide significantly enhanced binding characteristics compared to isolated ligands. Here, we assess the ability of substrate-modified enzymatic activity. Energy transfer assays allowed quantitative, real-time measurement proteolytic digestion at polyvalent quantum dot-peptide conjugates. Enzymatic progress curves were analyzed using an integrated Michaelis–Menten (MM) formalism, revealing mechanistic details, including...
Botulinum neurotoxins (BoNTs) are extremely potent bacterial toxins that contaminate food supplies along with having a high potential for exploitation as bioterrorism agents. There is continuing need to rapidly and sensitively detect exposure these verify their active state, the latter directly affects diagnosis helps provide effective treatments. We investigate use of semiconductor quantum dot (QD)−peptide Förster resonance energy transfer (FRET) assemblies monitor activity BoNT serotype A...
The cannabinoid 1 receptor (CB1R) is one of the most widely expressed metabotropic G protein-coupled receptors in brain, and its participation various (patho)physiological processes has made CB1R activation a viable therapeutic modality. Adverse psychotropic effects limit clinical utility orthosteric agonists have promoted search for positive allosteric modulators (PAMs) with promise improved drug-like pharmacology enhanced safety over typical agonists. In this study, we describe synthesis...
Reported in this contribution are the synthesis, characterization, and charge transport properties of wire-like Ru2(ap)4(OPEn), where ap is 2-anilinopyridinate OPE −(C⋮CC6H4)nSCH2CH2SiMe3 with n = 1 (1) 2 (2). Scanning tunneling microscopy (STM) measurements compound inserted into a SAM C11 thiol reveal that molecule exhibits (i) stochastic switching characteristic wire molecules embedded insulating SAMs (ii) higher conductivity than SAM. More importantly, analysis molecular electronic decay...
The first total synthesis of (+)-Na-methyl-16-epipericyclivine (9) was completed [from d-(+)-tryptophan methyl ester] in an overall yield 42% (eight reaction vessels). optical rotation [[α]D +22.8 (c 0.50, CHCl3)] obtained on this material confirmed that the reported 0 CHCl3)]47 biogenetically unreasonable. syntheses (+)-vellosimine, (+)-normacusine B, (−)-alkaloid Q3, (−)-panarine, and (+)-Na-methylvellosimine are also described. Moreover, a mixed sample (1:1) synthetic (−)-panarine natural...
On the surface of a quantum dot (QD), maltose-binding protein (MBP, white and yellow in Figure) labeled with cyanine dye (red) self-assembles, resulting F?rster resonance energy transfer between acceptor QD donor. Upon binding maltose, MBP undergoes conformational change (white ⇌ yellow), causing concentration-dependent photoluminescence changes. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2089/2005/c0722_s.pdf or from author. Please...
We characterized the resonance energy transfer interactions for conjugates consisting of QD donors self-assembled with three distinct fluorescent protein acceptors: two monomeric proteins, dsRed derivative mCherry or yellow and multi-chromophore b-phycoerythrin light harvesting complex. Using steady-state time-resolved fluorescence, we showed that nonradiative excitation in these can be described within Förster dipole-dipole formalism, efficiencies vary degree spectral overlap,...
Quantum dots (QDs) are loaded with a series of peptides and proteins increasing size, including <20 residue peptide, myoglobin, mCherry, maltose binding protein, which together cover range masses from <2.2 to approximately 44 kDa. Conjugation the surface dihydrolipoic acid-functionalized QDs is facilitated by polyhistidine metal affinity coordination. Increasing ratios dye-labeled self-assembled then bioconjugates separated analyzed using agarose gel electrophoresis. Fluorescent...
Crystallography, quantum chemistry and potentiometry of Zr( iv ) hydroxamate complexes: a combination tools to improve the development 89 Zr chelation for nuclear imaging.
We report the development of a quantum dot (QD)–peptide–fullerene (C60) electron transfer (ET)-based nanobioconjugate for visualization membrane potential in living cells. The bioconjugate is composed (1) central QD donor, (2) membrane-inserting peptidyl linker, and (3) C60 acceptor. photoexcited donor engages ET with acceptor, resulting quenching photoluminescence (PL) that tracks positively number moieties arrayed around QD. nature QD-capping ligand also modulates efficiency; neutral...
Treatments for autoimmunity - diseases where the immune system mistakenly attacks self-molecules are not curative and leave patients immunocompromised. New studies aimed at more specific treatments reveal development of inflammation or tolerance is influenced by form self-antigens presented. Using a mouse model multiple sclerosis (MS), we show first time that quantum dots (QDs) can be used to generate immunological controlling density self-antigen on QDs. These assemblies display dense...
As a specific example of the enhancement enzymatic activity that can be induced by nanoparticles, we investigate hydrolysis organophosphate paraoxon phosphotriesterase (PTE) when latter is displayed on semiconductor quantum dots (QDs). PTE conjugation to QDs underwent extensive characterization including structural simulations, electrophoretic mobility shift assays, and dynamic light scattering confirm orientational ratiometric control over enzyme display which appears necessary for...
Metagenomic and metaproteomic analyses were utilized to determine the composition function of complex air–water interface biofilms sampled from hulls two US Navy destroyers. Prokaryotic community using PhyloChip-based 16S rDNA profiling revealed significantly different taxonomically rich biofilm communities (6,942 taxa) in which majority unique taxa ascribed members Gammaproteobacteria, Alphaproteobacteria Clostridia. Although metagenomic sequencing indicated that both dominated by...