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1.  Distinct Pathways Generate Peptides from Defective Ribosomal Products for CD8+ T Cell Immunosurveillance 
To understand better the endogenous sources of MHC class I peptide ligands, we generated an antigenic reporter protein whose degradation is rapidly and reversibly controlled with Shield-1, a cell-permeant drug. Using this system, we demonstrate that defective ribosomal products (DRiPs) represent a major and highly efficient source of peptides and are completely resistant to our attempts to stabilize the protein. Although peptides also derive from nascent Shield-1–sensitive proteins and “retirees” created by Shield-1 withdrawal, these are much less efficient sources on a molar basis. We use this system to identify two drugs—each known to inhibit polyubiquitin chain disassembly—that selectively inhibit presentation of Shield-1–resistant DRiPs. These findings provide the initial evidence for distinct biochemical pathways for presentation of DRiPs versus retirees and implicate polyubiquitin chain disassembly or the actions of deubiquitylating enzymes as playing an important role in DRiP presentation.
PMCID: PMC3408966  PMID: 21228349
2.  Carteriosulfonic Acids A-C, GSK-3β Inhibitors from a Carteriospongia sp 
Journal of natural products  2009;72(9):1651-1656.
Modulators of Wnt signaling have therapeutic potential in a number of human diseases. A fractionated library from marine invertebrates was screened in a luciferase assay designed to identify modulators of Wnt signaling. A fraction from a Carteriospongia sp. sponge activated Wnt signaling and was subsequently shown to inhibit GSK-3β, which inhibits Wnt signaling through phosphorylation of β-catenin. Three novel natural products, carteriosulfonic acids A (1), B (2) and C (3), were identified as active constituents. The carteriosulfonic acids contain unprecedented 4,6,7,9-tetrahydroxylated decanoic acid subunits. Their structures were elucidated through analysis of NMR data and a detailed analysis of pseudo MS3 spectra.
PMCID: PMC2754322  PMID: 19778090
3.  Psammaplin A as a general activator of cell based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives 
Bioorganic & medicinal chemistry  2008;17(6):2189-2198.
The Wnt signaling pathway regulates cell growth and development in metazoans, and is therefore of interest for drug discovery. By screening a library of 5,808 pre-fractionated marine extracts in a cell-based Wnt signaling assay, several signaling activators and inhibitors were observed. LCMS based fractionation rapidly identified an active compound from Pseudoceratina purpurea as psammaplin A, a known HDAC inhibitor. Other HDAC inhibitors similarly activated signaling in this assay, indicating HDAC inhibitors will be identified through many cell-based reporter assays. In a large scale analysis of P. purpurea, three previously undescribed bromotyrosine based natural products were identified; the structure of one of these was confirmed by synthesis. Additionally, three other derivatives of psammaplin A were prepared: a mixed disulfide and two sulfinate esters. Finally, evidence to support a structural reassignment of psammaplin I from a sulfone to the isomeric sulfinate ester is presented.
PMCID: PMC2670876  PMID: 19022675
4.  Oppositines A and B, Sesquiterpene Pyridine Alkaloids from a Sri Lankan Pleurostylia opposita 
Journal of natural products  2006;69(12):1833-1835.
Two new sesquiterpene pyridine alkaloids, oppositines A (1) and B (2), have been isolated from the plant, Pleurostylia opposita (Celastraceae), collected in Sri Lanka. The compounds were isolated and purified by solvent/solvent partitioning, column chromatography and HPLC. Their structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Oppositines A (1) and B (2) showed moderate cytotoxicity against HCT116 cell lines with EC50 values of 27 ± 2 and 26 ± 3 μM, respectively.
PMCID: PMC2533843  PMID: 17190474
5.  Chemical Transformation of Prostaglandin-A2: A Novel Series of C-10 Halogenated, C-12 Hydroxylated Prostaglandin-A2 Analogues 
Organic letters  2006;8(10):2171-2174.
Synthesis of a novel class of C-10 halogenated and C-12 oxygenated prostaglandin-A2 derivatives 6(a–c) has been accomplished. (15S)-Prostaglandin-A2 (1), from the gorgonian Plexaura homomalla, served as the starting material for the synthesis. The absolute configuration was determined using NMR.
PMCID: PMC2533845  PMID: 16671809

Results 1-5 (5)