A5058261985- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Biochemical and Structural Characterization
- Synthesis and Biological Evaluation
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Microbial Metabolism and Applications
- bioluminescence and chemiluminescence research
- Mosquito-borne diseases and control
- HIV Research and Treatment
- DNA and Nucleic Acid Chemistry
- Diabetes and associated disorders
- Glycosylation and Glycoproteins Research
- Tuberculosis Research and Epidemiology
- Receptor Mechanisms and Signaling
- Biotin and Related Studies
- Protease and Inhibitor Mechanisms
- Computational Drug Discovery Methods
- Galectins and Cancer Biology
- Pancreatic function and diabetes
- Insect symbiosis and bacterial influences
- CAR-T cell therapy research
- Oceanographic and Atmospheric Processes
University of Florida
2024
Scripps Research Institute
2015-2020
Jupiter Medical Center
2015-2020
Yale University
2010-2014
Cornell University
2005
Monterey Bay Aquarium Research Institute
2005
University of Rhode Island
2005
The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. very molecular features confer binding potency and specificity, such as stereochemistry, regiochemistry, scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces redundancy diverse scaffolds...
The circulating antibody repertoire encodes a patient's health status and pathogen exposure history, but identifying antibodies with diagnostic potential usually requires knowledge of the antigen(s). We previously circumvented this problem by screening libraries bead-displayed small molecules against case control serum samples to discover "epitope surrogates" (ligands IgGs enriched in sample). Here, we describe an improved version technology that employs DNA-encoded high-throughput...
There is great interest in the development of probe molecules and drug leads that would bind tightly selectively to protein surfaces are difficult target with traditional molecules, such as those involved protein-protein interactions. The currently available evidence suggests this will require larger have quite different chemical properties than typical Lipinski-compliant enzyme active sites. We describe here efforts develop vast libraries conformationally constrained oligomers a potentially...
Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as major public health threat. Here we report the cell wall of S. can be covalently re-engineered to contain non-native small molecules. This process makes use endogenous levels enzyme sortase A (SrtA), which ordinarily functions incorporate proteins into wall. Thus, incubation wild-type bacteria with rationally designed SrtA substrates results in covalent incorporation functional molecular handles...
This article reports the design, synthesis, and evaluation of a novel class molecules intermediate size (approximately 7000 Da), which possess both targeting effector functions antibodies. These compounds—called synthetic antibody mimics prostate cancer (SyAM-Ps)—bind simultaneously to prostate-specific membrane antigen Fc gamma receptor I, thus eliciting highly selective cell phagocytosis. SyAMs have potential combine advantages small-molecule biologic therapies, may address many drawbacks...
Dense accumulations of certain phytoplankton make the ocean appear reddish.Some these "red tides" poison marine life and negatively impact coastal fi sheries human health.Complex variability in waters coupled with rudimentary understanding ecology challenge our ability to understand predict red tides.During fall 2002, multi-scale physical biological observations were made preceding during a tide bloom Monterey Bay, California.These intensive provided insight into oceanography underlying...
Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library 508,032 synthetic, non-natural oligomers, we selected characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based bead screening was used select bound IgG from ZIKV-immune but not dengue-immune sera. Deep...
Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy target metastatic cancer cells immune-mediated destruction targeting urokinase-type plasminogen activator receptor (uPAR). Urokinase-type (uPA) and uPAR are overexpressed on surfaces of wide range invasive believed contribute substantially migratory propensities these cells. The key component our approach is...
A screen of a DNA-encoded library PICCOs was screened against streptavidin (SA) resulting in the isolation high affinity ligand.
Autoantibodies raised against β cell antigens are the most reliable preclinical biomarkers for predicting imminent onset of type 1 diabetes mellitus (T1DM). The current detection platforms technically challenging or run on clinically esoteric equipment. Here, we present a straightforward approach to detect autoantibody that employs highly PEGylated microspheres onto which mounted various capture agents include affinity-tagged small molecule "antigen surrogates." After incubation with...
DNA-Encoded Libraries (DEL) are combinatorial small molecule libraries that offer an efficient way to characterize diverse chemical spaces. Selection experiments using DELs pivotal drug discovery efforts, enabling high-throughput screens for hit finding. However, limited availability of public DEL datasets hinders the advancement computational techniques designed process such data. To bridge this gap, we present KinDEL, one first large, publicly available on two kinases: Mitogen-Activated...
ADVERTISEMENT RETURN TO ISSUEPREVAddition, Retraction...Addition, Retraction, CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to A Biosynthetic Strategy for Re-engineering the Staphylococcus aureus Cell Wall with Non-native Small MoleculesJames W. Nelson, Alexander G. Chamessian, Patrick J. McEnaney, Ryan P. Murelli, Barbara I. Kazmierczak, and David A. Spiegel*Cite this: ACS Chem. Biol. 2011, 6, 9, 971Publication Date (Web):August 30, 2011Publication History Published...
Abstract Review: 125 refs.