A5090942677- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- HIV Research and Treatment
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Microbial Natural Products and Biosynthesis
- Synthetic Organic Chemistry Methods
- Tryptophan and brain disorders
- Microtubule and mitosis dynamics
- Synthesis and Characterization of Heterocyclic Compounds
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
- Organoselenium and organotellurium chemistry
- Synthesis and Biological Evaluation
- Advanced Breast Cancer Therapies
- Organophosphorus compounds synthesis
- Glycosylation and Glycoproteins Research
- Synthesis and Reactivity of Heterocycles
- Synthesis and biological activity
- Synthesis of heterocyclic compounds
- Stress Responses and Cortisol
- Insect and Pesticide Research
- Pharmacological Receptor Mechanisms and Effects
- Cancer therapeutics and mechanisms
- Genomics, phytochemicals, and oxidative stress
Bristol-Myers Squibb (Germany)
2010-2023
Bristol-Myers Squibb (United States)
2002-2021
DuPont (United States)
1992-2006
Experimental Station
1997-2006
Wilmington University
1993-2006
The University of Texas Health Science Center at San Antonio
1993
Harvard University
1987-1988
Harvard University Press
1984
University of Pennsylvania
1979-1981
Significance Indoleamine 2,3-dioxygenase (IDO1) is a heme protein that catalyzes the dioxygenation of tryptophan. Cells expressing this activity are able to profoundly alter their surrounding environment suppress immune response. Cancer cells exploit pathway avoid immune-mediated destruction. Through range kinetic, structural, and cellular assays, we show two classes highly selective inhibitors IDO1 act by competing with binding apo-IDO1. This shows dynamically bound its cofactor in what...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA mild and general method for the synthesis of 0-glycosidesK. C. Nicolaou, S. P. Seitz, D. PapahatjisCite this: J. Am. Chem. Soc. 1983, 105, 8, 2430–2434Publication Date (Print):April 1, 1983Publication History Published online1 May 2002Published inissue 1 April 1983https://pubs.acs.org/doi/10.1021/ja00346a053https://doi.org/10.1021/ja00346a053research-articleACS PublicationsRequest reuse permissionsArticle Views1773Altmetric-Citations247LEARN...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-Phenylselenophthalimide (N-PSP) and N-phenylselenosuccinimide (N-PSS). Two versatile carriers of the phenylseleno group. Oxyselenation olefins a selenium-based macrolide synthesisK. C. Nicolaou, D. A. Claremon, W. E. Barnette, S. P. SeitzCite this: J. Am. Chem. Soc. 1979, 101, 13, 3704–3706Publication Date (Print):June 1, 1979Publication History Published online1 May 2002Published inissue 1 June...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhenylseleno- and phenylsulfenolactonizations. Two highly efficient synthetically useful cyclization proceduresK. C. Nicolaou, S. P. Seitz, W. J. Sipio, F. BlountCite this: Am. Chem. Soc. 1979, 101, 14, 3884–3893Publication Date (Print):July 1, 1979Publication History Published online1 May 2002Published inissue 1 July 1979https://pubs.acs.org/doi/10.1021/ja00508a028https://doi.org/10.1021/ja00508a028research-articleACS PublicationsRequest reuse...
High-resolution X-ray structures of the complexes HIV-1 protease (HIV-1PR) with peptidomimetic inhibitors reveal presence a structural water molecule which is hydrogen bonded to both mobile flaps enzyme and two carbonyls flanking transition-state mimic inhibitors. Using structure−activity relationships C2-symmetric diol inhibitors, computed-aided drug design tools, first principles, we designed synthesized novel class cyclic ureas that incorporates this preorganizes side chain residues into...
Efavirenz (Sustiva, Fig. 1) is a potent and specific inhibitor of HIV-1 reverse transcriptase approved for the treatment HIV infection. To examine potential differences in metabolism among species, liquid chromatography/mass spectrometry profiles efavirenz metabolites urine rats, guinea pigs, hamsters, cynomolgus monkeys, humans were obtained compared. The isolated, structures determined unequivocally by mass spectral NMR analyses. was metabolized extensively all species as evidenced...
In developing inhibitors of the LIM kinases, initial lead molecules combined potent target inhibition with cytotoxic activity. However, as subsequent compounds were evaluated, activity separated from kinases. A rapid determination mechanism and its molecular was enabled by integrating data two robust core technologies. High-content assays gene expression profiling both indicated an effect on microtubule stability. Although are still kinase inhibitors, their structures did not predict tubulin...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of macrocycles by intramolecular ketophosphonate reactions. Stereoselective construction the "left-wing" carbomycin B and a synthesis dl-muscone from oleic acidK. C. Nicolaou, S. P. Seitz, M. R. Pavia, N. A. PetasisCite this: J. Org. Chem. 1979, 44, 22, 4011–4013Publication Date (Print):October 1, 1979Publication History Published online1 May 2002Published inissue 1 October...
The bacterial cell wall is a polymer consisting of alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) units, cross-linked via peptides appended to MurNAc. final steps in the formation wall, also referred as murein, are catalyzed by high-molecular-weight, class A penicillin-binding proteins (PBPs). These bifunctional enzymes catalyze both glycosyltransfer, form carbohydrate backbone transpeptidation, interstrand peptide linkages. Using PBP1b from Eschericia coli, an...
A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and originally prepare DMP 323. other two approaches use L-tartaric acid or L-mannitol as the material. required four contiguous R,S,S,R centers urea scaffold are introduced using substrate control methodology. Each has specific advantages based on desired P1/P1'...
Using a high-throughput screening strategy, series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation protein substrate with IC(50)s in low micromolar range. On basis preliminary structure-activity relationships (SAR), model proposed which these inhibitors occupy ATP-binding site enzyme, forming critical hydrogen bonds to same residue (Val96) amino group ATP is presumed bind....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 16-membered-ring macrolide antibiotics. 4. Carbomycin B and leucomycin A3: total synthesis cyclic key intermediateK. C. Nicolaou, M. R. Pavia, S. P. SeitzCite this: J. Am. Chem. Soc. 1981, 103, 5, 1224–1226Publication Date (Print):March 1, 1981Publication History Published online1 May 2002Published inissue 1 March 1981https://pubs.acs.org/doi/10.1021/ja00395a044https://doi.org/10.1021/ja00395a044research-articleACS PublicationsRequest...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbohydrates in organic synthesis. Synthesis of 16-membered-ring macrolide antibiotics. 5. Total synthesis O-mycinosyltylonolide: key intermediatesK. C. Nicolaou, M. R. Pavia, and S. P. SeitzCite this: J. Am. Chem. Soc. 1982, 104, 7, 2027–2029Publication Date (Print):April 1, 1982Publication History Published online1 May 2002Published inissue 1 April...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of aplasmomycinE. J. Corey, Duy H. Hua, Bai Chuan Pan, and Steven P. SeitzCite this: Am. Chem. Soc. 1982, 104, 24, 6818–6820Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://pubs.acs.org/doi/10.1021/ja00388a074https://doi.org/10.1021/ja00388a074research-articleACS PublicationsRequest reuse permissionsArticle Views977Altmetric-Citations73LEARN ABOUT THESE...
Samples of purple lipoxygenase prepared by addition either 13-hydroperoxy-9,11-octadecadienoic acid or linoleic and oxygen to ferric contain pentadienyl and/or peroxyl radicals. The radicals are identified the g values hyperfine splitting parameters natural abundance isotopically enriched samples. line shapes their EPR spectra suggest conformationally constrained when compared same generated in frozen acid. Further, unusually difficult saturate. stable buffered aqueous solution at 4 degrees...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbohydrates in organic synthesis. Synthesis of 16-membered-ring macrolide antibiotics. 6. Total synthesis O-mycinosyltylonolide: coupling key intermediates and macrocyclizationK. C. Nicolaou, S. P. Seitz, M. R. PaviaCite this: J. Am. Chem. Soc. 1982, 104, 7, 2030–2031Publication Date (Print):April 1, 1982Publication History Published online1 May 2002Published inissue 1 April...
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTIndenopyrazoles as Novel Cyclin Dependent Kinase (CDK) InhibitorsDavid A. Nugiel, Ana-Marie Etzkorn, Anup Vidwans, Pamela Benfield, Michael Boisclair, Catherine R. Burton, Sarah Cox, Phillip M. Czerniak, Deborah Doleniak, and Steven P. SeitzView Author Information The DuPont Pharmaceuticals Company, Box 80336, Wilmington, Delaware 19880-0336 Cite this: J. Med. Chem. 2001, 44, 9, 1334–1336Publication Date (Web):April 19, 2001Publication History...
We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in ATP pocket. A unique combination active pharmacophores led us semicarbazide-based inhibitors highly potent against CDK2 CDK4 while maintaining selectivity other relevant serine/threonine kinases. These were transformed human colon cancer...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructural Characterization of Alkyl and Peroxyl Radicals in Solutions Purple LipoxygenaseMark J. Nelson, Rebecca A. Cowling, Steven P. SeitzCite this: Biochemistry 1994, 33, 16, 4966–4973Publication Date (Print):April 1, 1994Publication History Published online1 May 2002Published inissue 1 April 1994https://pubs.acs.org/doi/10.1021/bi00182a027https://doi.org/10.1021/bi00182a027research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 16-membered-ring macrolide antibiotics. 3. Carbomycin B and leucomycin A3: retrosynthetic studiesK. C. Nicolaou, S. P. Seitz, M. R. PaviaCite this: J. Am. Chem. Soc. 1981, 103, 5, 1222–1224Publication Date (Print):March 1, 1981Publication History Published online1 May 2002Published inissue 1 March 1981https://pubs.acs.org/doi/10.1021/ja00395a043https://doi.org/10.1021/ja00395a043research-articleACS PublicationsRequest reuse...