A5051707773- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- HIV/AIDS drug development and treatment
- DNA and Nucleic Acid Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- HIV Research and Treatment
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Structure and Dynamics
- Fluorine in Organic Chemistry
- Galectins and Cancer Biology
- Enzyme Structure and Function
- Pneumocystis jirovecii pneumonia detection and treatment
- Immunotherapy and Immune Responses
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Analytical Chemistry and Chromatography
- Protein Kinase Regulation and GTPase Signaling
- Microbial Natural Products and Biosynthesis
- Computational Drug Discovery Methods
National Cancer Institute
2013-2023
Frederick National Laboratory for Cancer Research
2012-2023
Center for Cancer Research
2013-2023
National Institutes of Health
1999-2017
Molecular Discovery (United Kingdom)
2010
University of Maryland, Baltimore
2004-2008
Science Applications International Corporation (United States)
2004-2007
United States Food and Drug Administration
2006
Center for Drug Evaluation and Research
2006
National Institute of Diabetes and Digestive and Kidney Diseases
2004
Approximately 1 million people in the United States suffer from interstitial cystitis, a chronic painful urinary bladder disorder characterized by thinning or ulceration of epithelial lining; its etiology is unknown. We have identified glycosylated frizzled-related peptide inhibitor cell proliferation that secreted specifically cells patients with this disorder. This antiproliferative factor (APF) profoundly inhibits means regulation adhesion protein and growth production. The structure APF...
The development of vaccines against specific types cancers will offer new modalities for therapeutic intervention. Here, we describe the synthesis a novel vaccine construction prepared from spherical gold nanoparticles 3–5 nm core diameters. particles were coated with both tumor-associated glycopeptides antigens containing cell-surface mucin MUC4 Thomsen Friedenreich (TF) antigen attached at different sites and 28-residue peptide complement derived protein C3d to act as B-cell activating...
Riboswitches are naturally occurring RNA aptamers that regulate gene expression by binding to specific small molecules. control the of essential bacterial genes and important models for RNA-small molecule recognition. Here, we report discovery a class synthetic molecules bind PreQ1 riboswitch aptamers. These specifically reversibly with high affinity induce conformational change. Furthermore, ligands modulate activity through transcriptional termination despite no obvious chemical similarity...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTFormation of Short, Stable Helices in Aqueous Solution by β-Amino Acid HexamersDaniel H. Appella, Joseph J. Barchi,, Stewart R. Durell, and Samuel GellmanView Author Information Department Chemistry, University Wisconsin Madison, 53706 Laboratory Medicinal Chemistry Experimental Computational Biology Division Basic Sciences, National Cancer Institute Bethesda, Maryland 20892 Cite this: Am. Chem. Soc. 1999, 121, 10, 2309–2310Publication Date...
It has been proposed that the preference of 3‘-azido-3‘-deoxythymidine (AZT) for extreme 3E (south) conformation, as observed in its X-ray structure, is responsible potent anti-HIV activity. However, it also suggested antipodal north conformation may be required strong interaction AZT 5‘-triphosphate with target enzyme, HIV reverse transcriptase (RT). To resolve this issue, we have constructed two conformationally rigid carbocyclic analogues which are locked permanently into opposite 2E...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcutiphycin and 20,21-didehydroacutiphycin, new antineoplastic agents from the cyanophyte Oscillatoria acutissimaJoseph J. Barchi Jr., Richard E. Moore, Gregory M. L. PattersonCite this: Am. Chem. Soc. 1984, 106, 26, 8193–8197Publication Date (Print):December 1, 1984Publication History Published online1 May 2002Published inissue 1 December 1984https://pubs.acs.org/doi/10.1021/ja00338a031https://doi.org/10.1021/ja00338a031research-articleACS...
We have developed a novel antigen delivery system based on polysaccharide-coated gold nanoparticles (AuNPs) targeted to antigen-presenting cells (APCs) expressing Dectin-1. AuNPs were synthesized de novo using yeast-derived β-1,3-glucans (B13G) as the reductant and passivating agent in microwave-catalyzed procedure, yielding highly uniform serum-stable particles. These further functionalized with both peptide specific glycosylated form from tandem repeat sequence of mucin 4 (MUC4),...
Fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting are lacking. Here, we screen 62,643 compounds using engineered cell line that monitors transcriptional activity identifying a hitherto uncharacterized compound, P3FI-63. RNA-seq, ATAC-seq, and docking analyses implicate histone lysine demethylases (KDMs) as its targets. Enzymatic assays confirm inhibition of multiple KDMs with highest...
Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4 + or GSL-depleted cells rendered those susceptible HIV-1 envelope glycoprotein-mediated cell fusion. Individual components in GSL mixture were isolated by fractionation on a silica-gel column and incorporated into membranes cells. GSL-supplemented target then examined for their ability fuse with TF228 expressing LAI glycoprotein. We found one fraction, fraction 3, exhibited highest recovery...
The conformational properties of β-peptides comprised enantiomerically pure trans-2-aminocyclohexanecarboxylic acid (ACHC) or trans-2-aminocyclopentanecarboxylic (ACPC) units were studied by NMR spectroscopy in organic solvents. In pyridine-d5 solution, ACPC hexamer 1 and octamer 2 displayed well-defined helical structures characterized a series 12-membered hydrogen-bonded rings ("12-helix"). solution calculated from the NMR-derived constraints very similar to conformations found previously...
Two isomers of methanocarba (MC) thymidine (T), one an effective antiherpes agent with the pseudosugar moiety locked in North (N) hemisphere pseudorotational cycle (1a, N-MCT) and other inactive isomer antipodean South (S) conformation (1b, S-MCT) were used to determine whether kinases polymerases discriminate between their substrates on basis sugar conformation. A combined solid-state solution conformational analysis both compounds, coupled direct measurement mono-, di-, triphosphate levels...
Abstract
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAbsolute stereochemistry of palytoxinRichard E. Moore, Giovanni Bartolini, Joseph Barchi, Aksel A. Bothner-By, Josef Dadok, and FordCite this: J. Am. Chem. Soc. 1982, 104, 13, 3776–3779Publication Date (Print):June 1, 1982Publication History Published online1 May 2002Published inissue 1 June 1982https://pubs.acs.org/doi/10.1021/ja00377a064https://doi.org/10.1021/ja00377a064research-articleACS PublicationsRequest reuse permissionsArticle...
17-Dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and 17-allylamino-17-demethoxygeldanamycin (17-AAG) are two derivatives of geldanamycin (GA) that currently undergoing clinical evaluation as anticancer agents. These agents bind to heat shock protein 90 (hsp90), resulting in the destabilization client proteins inhibition tumor growth. In a search for mechanism hepatotoxicity, which is dose-limiting toxicity these agents, we found GA its derivatives, 17-AAG 17-DMAG, react chemically...
Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In study, we demonstrate that many common peptide coupling conditions used prepare O-linked result substantial amounts epimerization at α position. fact, resulted up 80% non-natural epimer, indicating it can be major product some reactions. Through a series mechanistic studies, enhanced...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformationally Locked Nucleoside Analogs. Synthesis of Dideoxycarbocyclic Analogs Structurally Related to Neplanocin CJuan B. Rodriguez, Victor E. Marquez, Marc C. Nicklaus, Hiroaki Mitsuya, and Joseph J. Barchi Jr.Cite this: Med. Chem. 1994, 37, 20, 3389–3399Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://doi.org/10.1021/jm00046a024RIGHTS & PERMISSIONSArticle...
We have prepared glycosylated analogues of the principal neutralizing determinant gp120 and studied their conformations by NMR circular dichroism spectroscopies. The 24-residue peptide from HIV-1IIIB isolate (residues 308−331) designated RP135, which contains immunodominant tip V3 loop, was with both N- O-linked sugars. structures two glycopeptides, one an N-linked β-glucosamine (RP135NG) other α-galactosamine units (RP135digal), were Molecular dynamics calculations based on data obtained in...
2(1H)-Pyrimidinone riboside (zebularine, 1b) and its 5-fluoro (6b) 2'-ara-fluoro (7b) analogues have been synthesized evaluated in vivo as antitumor agents. Zebularine provides increase life span (ILS) values of ca. 70% against intraperitoneal (ip) murine B16 melanoma 50% P388 leukemia. This compound is active when administered either ip or orally subcutaneously implanted L1210 leukemia, producing ILS about 100% at an optimum dose 400 mg/kg. 1b also (60% ILS) ara-C-resistant L1210. The...
Glycan-binding proteins are important for a wide variety of basic research and clinical applications, but with high affinity selectivity carbohydrates difficult to obtain. Here we describe facile cost-effective strategy generate monoclonal lamprey antibodies, called lambodies, that target glycan determinants. We screened library yeast surface-displayed (YSD) variable lymphocyte receptors (VLR) clones can selectively bind various biomedically glycotopes. These glycoconjugates included...
We investigated how many cases of the same chemical sold as different products (at possibly prices) occurred in a prototypical large aggregated database and simultaneously tested tautomerism definitions chemoinformatics toolkit CACTVS. applied standard CACTVS tautomeric transforms plus set recently developed ring-chain to Aldrich Market Select (AMS) 6 million screening samples building blocks. In 30 000 cases, two or more AMS were found be just forms compound. purchased analyzed 166 such...
Abstract The backbone dynamics of the immunoglobulin‐binding domain (Bl) streptococcal protein G, uniformly labeled with 15 N, have been investigated by two‐dimensional inverse detected heteronuclear 1 H‐ N NMR spectroscopy at 500 and 600 MHz. T , 2 nuclear Overhauser enhancement data were obtained for all 55 NH vectors B1 both field strengths. overall correlation time from an analysis / ratios was 3.3 ns 26 °C. Overall, is a relatively rigid protein, consistent fact that over 95% residues...