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Your search keyword '"Kuai-lin Sun"' showing total 11 results
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11 results on '"Kuai-lin Sun"'

1. A novel micellular fluorogenic substrate for quantitating the activity of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma (PLCγ) enzymes.

Author

Ramya Visvanathan, Tadanobu Utsuki, Daniel E Beck, W Brent Clayton, Emma Lendy, Kuai-Lin Sun, Yinghui Liu, Kirk W Hering, Andrew Mesecar, Zhong-Yin Zhang, and Karson S Putt

Subjects
Medicine, Science
Abstract

The activities of the phospholipase C gamma (PLCγ) 1 and 2 enzymes are essential for numerous cellular processes. Unsurprisingly, dysregulation of PLCγ1 or PLCγ2 activity is associated with multiple maladies including immune disorders, cancers, and neurodegenerative diseases. Therefore, the modulation of either of these two enzymes has been suggested as a therapeutic strategy to combat these diseases. To aid in the discovery of PLCγ family enzyme modulators that could be developed into therapeutic agents, we have synthesized a high-throughput screening-amenable micellular fluorogenic substrate called C16CF3-coumarin. Herein, the ability of PLCγ1 and PLCγ2 to enzymatically process C16CF3-coumarin was confirmed, the micellular assay conditions were optimized, and the kinetics of the reaction were determined. A proof-of-principle pilot screen of the Library of Pharmacologically Active Compounds 1280 (LOPAC1280) was performed. This new substrate allows for an additional screening methodology to identify modulators of the PLCγ family of enzymes.

Published
2024
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2. A novel fluorogenic reporter substrate for 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2): Application to high-throughput screening for activators to treat Alzheimer's disease

Author

Ramya Visvanathan, Tadanobu Utsuki, Daniel E. Beck, Emma Lendy, Kuai-lin Sun, Yinghui Liu, Kirk W. Hering, Andrew Mesecar, Zhong-Yin Zhang, and Karson S. Putt

Subjects
Alzheimer's disease, Phospholipase C, PLCG2, C8CF3-coumarin, Turn-on fluorophore, High throughput screening, Medicine (General), R5-920, Biotechnology, TP248.13-248.65
Abstract

A rare coding variant in PLCγ2 (P522R) expressed in microglia induces a mild activation of enzymatic activity when compared to wild-type. This mutation is reported to be protective against the cognitive decline associated with late-onset Alzheimer's disease (LOAD) and therefore, activation of wild-type PLCγ2 has been suggested as a potential therapeutic target for the prevention and treatment of LOAD. Additionally, PLCγ2 has been associated with other diseases such as cancer and some autoimmune disorders where mutations with much greater increases in PLCγ2 activity have been identified. Here, pharmacological inhibition may provide a therapeutic effect. In order to facilitate our investigation of the activity of PLCγ2, we developed an optimized fluorogenic substrate to monitor enzymatic activity in aqueous solution. This was accomplished by first exploring the spectral properties of various “turn-on” fluorophores. The most promising turn-on fluorophore was incorporated into a water-soluble PLCγ2 reporter substrate, which we named C8CF3-coumarin. The ability of PLCγ2 to enzymatically process C8CF3-coumarin was confirmed, and the kinetics of the reaction were determined. Reaction conditions were optimized to identify small molecule activators, and a pilot screen of the Library of Pharmacologically Active Compounds 1280 (LOPAC1280) was performed with the goal of identifying small molecule activators of PLCγ2. The optimized screening conditions allowed identification of potential PLCγ2 activators and inhibitors, thus demonstrating the feasibility of this approach for high-throughput screening.

Published
2023
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5. Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors

Author

Yuntao Song, Jeffrey C. Hanselman, Xue-Min Cheng, Scott D. Larsen, Zhiwu Lin, Bharat K. Trivedi, Graeme Bainbridge, Alexander Pavlovsky, Larry D. Bratton, Andrew Robertson, Paul C. Unangst, Jeffrey A. Pfefferkorn, Melissa S. Harris, Lisa Dillon, Bruce Auerbach, Erasga Noe Ouano, Chitase Lee, Chulho Choi, Karl Olsen, Catherine Sekerke, Toni Jo Poel, Nicole Caspers, Matthias Eberstadt, Kuai Lin Sun, Steven R. Miller, Roderick Joseph Sorenson, Gina Lu, Valerie Askew, Thomas E. Mertz, and Huifen Chen

Subjects
Models, Molecular, Statin, medicine.drug_class, Clinical Biochemistry, Pharmaceutical Science, Hyperlipidemias, Reductase, Biochemistry, Chemical synthesis, Structure-Activity Relationship, Cricetinae, Drug Discovery, medicine, Animals, Structure–activity relationship, Pyrroles, Rosuvastatin Calcium, Molecular Biology, chemistry.chemical_classification, Sulfonamides, Dose-Response Relationship, Drug, Molecular Structure, biology, Organic Chemistry, Hydroxymethylglutaryl-CoA reductase, Fluorobenzenes, Pyrimidines, Enzyme, Liver, chemistry, Enzyme inhibitor, Drug Design, HMG-CoA reductase, biology.protein, Molecular Medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors
Abstract

This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.

Published
2007
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6. A simple method for preparation of N-mono- and N,N-di-alkylated α-amino acids

Author

Anthony D. Sercel, Kuai-Lin Sun, Yuntao Song, Bruce D. Roth, Norman L. Colbry, and D. R. Johnson

Subjects
chemistry.chemical_classification, Chemistry, Reductive methylation, Organic Chemistry, Drug Discovery, lipids (amino acids, peptides, and proteins), Alkylation, Biochemistry, Medicinal chemistry, Amino acid, Catalysis
Abstract

Reactions of α-amino acids with ketones under hydrogenation conditions using 20% Pd(OH) 2 /C as the catalyst gave N -mono-alkylated amino acids in high yields. Reductive methylation of N -mono-alkylated amino acids under the same hydrogenation conditions at 50°C afforded N , N -di-alkylated amino acids in excellent yields. This simple method has been used to synthesize N -mono- and N , N -di-alkylated amino acids on a scale of 200 g.

Published
2000
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7. ChemInform Abstract: Structure of Hymenoratin

Author

P. W. Baures, D. S. Eggleston, Kuai-Lin Sun, and J. A. Chan

Subjects
Chemistry, Stereochemistry, Nanotechnology, General Medicine
Abstract

C 15 H 22 O 4 cristallise dans P2 1 avec a=13.525, b=7.549, c=13.646A, β=90.02°, Z=4, T=225K; affinement jusqu'a R=0.046. Dans ce compose, le cycle a sept chainons est fusionne de maniere cis au α-methylene-γ-lactone. La conformation du cycloheptane est un bateau legerement deforme. Le cycle lactone adopte une conformation enveloppe. On note la presence d'un contact intramoleculaire O3'-O4' de 3.070A. C'est la disparite des liaisons hydrogene auxquelles participent les molecules qui les distinguent l'une de l'autre

Published
2010
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8. Development of a Practical Synthesis of Novel, Pyrrole-Based HMG-CoA Reductase Inhibitors

Author

Steven R. Miller, Scott D. Larsen, Yuntao Song, David C. Boyles, Jeffrey A. Pfefferkorn, Chulho Choi, William Kissel, Bharat K. Trivedi, Daniel Merritt Bowles, and Kuai Lin Sun

Subjects
chemistry.chemical_classification, biology, Stereochemistry, Organic Chemistry, Cardiac activity, General Medicine, Reductase, Biochemistry, Combinatorial chemistry, Pyrrole derivatives, chemistry.chemical_compound, chemistry, Ylide, Drug Discovery, HMG-CoA reductase, Side chain, biology.protein, Pyrrole
Abstract

This paper describes the development of an efficient and scalable second generation synthesis of novel, pyrrole-based HMG-CoA reductase inhibitors. Compound 1 was identified as part of a discovery program aimed at finding improved treatments for hypercholesterolemia. Herein, we describe an efficient synthesis of its highly functionalized pyrrole core followed by attachment of the 3,5-dihydroxyhexanoic acid side chain via ylide olefination chemistry.

Published
2007
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9. ChemInform Abstract: A Simple Method for Preparation of N-Mono- and N,N-Di-alkylated α-Amino Acids

Author

Anthony D. Sercel, Bruce D. Roth, D. R. Johnson, Yuntao Song, Kuai-Lin Sun, and Norman L. Colbry

Subjects
chemistry.chemical_classification, Chemistry, Reductive methylation, Organic chemistry, lipids (amino acids, peptides, and proteins), General Medicine, Alkylation, Medicinal chemistry, Catalysis, Amino acid
Abstract

Reactions of α-amino acids with ketones under hydrogenation conditions using 20% Pd(OH) 2 /C as the catalyst gave N -mono-alkylated amino acids in high yields. Reductive methylation of N -mono-alkylated amino acids under the same hydrogenation conditions at 50°C afforded N , N -di-alkylated amino acids in excellent yields. This simple method has been used to synthesize N -mono- and N , N -di-alkylated amino acids on a scale of 200 g.

Published
2001
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10. Structure of hymenoratin

Author

P. W. Baures, Kuai-Lin Sun, J. A. Chan, and D. S. Eggleston

Subjects
chemistry.chemical_classification, Crystallography, chemistry.chemical_compound, Chemistry, Diol, X-ray crystallography, Molecule, General Medicine, Crystal structure, General Biochemistry, Genetics and Molecular Biology, Lactone
Abstract

C 15 H 22 O 4 cristallise dans P2 1 avec a=13.525, b=7.549, c=13.646A, β=90.02°, Z=4, T=225K; affinement jusqu'a R=0.046. Dans ce compose, le cycle a sept chainons est fusionne de maniere cis au α-methylene-γ-lactone. La conformation du cycloheptane est un bateau legerement deforme. Le cycle lactone adopte une conformation enveloppe. On note la presence d'un contact intramoleculaire O3'-O4' de 3.070A. C'est la disparite des liaisons hydrogene auxquelles participent les molecules qui les distinguent l'une de l'autre

Published
1992
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