Nanoparticles such as nanotubes, iron oxide, and gold can be made multifunctional (active targeting, biocompatible, drug-carrier, and traceable) by chemically modification of their surface. By targeting cancer cells, they can improve cancer diagnosis and treatment with a greater specificity. We use computer-assisted design of surface ligand molecules and parallel synthesis to make surface modified nanoparticle libraries for in vitro and in vivo studies. Lead nanomaterials with the desired properties are selected for further optimization.
Related recent publications:
Zhou, H.; Mu, Q.; Gao, N.; Liu, A.; Xing, Y.; Gao, S.; Zhang, Q.; Qu, G.; Chen, Y.; Liu, G.; Zhang, B.; Yan. B. A Nano-Combinatorial Library Strategy for the Discovery of Nanotubes with Reduced Protein-Binding, Cytotoxicity, and Immune Response, Nano Lett. 8(3), 859-865, 2008.
Mu, Q.; Liu, W.; Xing, Y.; Zhou, H.; Li, Z.; Zhang, Y.; Ji, L.; Wang, F.; Si, Z.; Zhang, B.; Yan, B. Protein Binding by Functionalized Multiwalled Carbon Nanotubes Is Governed by the Surface Chemistry of Both Parties and the Nanotube Diameter. J. Phys. Chem. C. 112(9), 3300-3307, 2008.
We generate molecular libraries using parallel synthesis and screen them for their anti-cancer activities. Screening hits are further optimized by medicinal chemistry and hit-follow-up library synthesis and screening. Our efforts focus on overcoming drug resistance and elucidating molecular mechanism.
Related recent publications:Zhou, H.; Wu, S.; Zhai, S.; Liu, A.; Sun, Y.; Li, R.; Zhang, Y.; Ekins, S.; Swaan, P. W.; Fang, B.; Zhang, B.; Yan, B.* Design, Synthesis, Cytoselective Toxicity, Structure-Activity Relationships, and Pharmacophore of Thiazolidinone Derivatives Targeting Drug-Resistant Lung Cancer Cells. J. Med. Chem. 51, 1242-1251, 2008.
Zhou, H.; Liu, A.; Li, X.; Ma, X.; Feng, W.; Zhang, W.; Yan, B.* Microwave-Assisted Fluorous Synthesis of 2-Aryl-Substituted 4-Thiazolidinone and 4-Thiazinanone Libraries. J. Comb. Chem. 10(2), 303-312, 2008.
High-throughput analysis and purification are key steps in drug discovery. Our High-throughput Analytical Chemistry Core Facility (link to HTAC Core pages) assists in the analysis and purification of compounds used for St. Jude drug discovery research and profiling of pharmaceutical properties of compounds. We investigate analytical issues in all phases of early drug discovery and develop novel methods and approaches to facilitate discovery.
Related recent publications:
Qi, M.; Zhou, H.; Ma, X.; Zhang, B.; Jefferies, C.; Yan, B. Feasibility of a Self-Calibrated LC/MS/UV Method to Determine the Absolute Amount of Compounds in Their Storage and Screening Lifecycle. J. Comb. Chem. 10 (2), 162-165, 2008.
Zhang, B.; Li, X.; Yan, B. Advances in HPLC detector-towards universal detection. Anal. Bioanal. Chem. 390(1), 299-301, 2008.
Yan, B., Shi, R., Zhang, B., Kshirsagar, T. A Kinetic Study of Product Cleavage Reactions from the Solid Phase by a Biocompatible and Removable Cleaving Reagent, HCl. J. Combi. Chem. 9(4), 684-689, 2007.
Yan, B. Zhao,J., Leopold, K., Zhang, B., Jiang, G. The Structure Dependent Response of Chemiluminescence Nitrogen Detector (CLND) for Organic Compounds with Adjacent Nitrogen Atoms Connected by a Single Bond. Anal. Chem. 79 (2) 718-726, 2007.
Irving, M., Krueger, C. A., Wade, J. V., Hodges, J. C., Leopold, K., Chan, C., Shaqair, S., Shornikov, A., Stock, M., Collins, N., Yan, B. High-Throughput Purification of Combinatorial Libraries II: Automated Separation of Single Diastereomers from a 1920-Member 4-Amidopyrrolidinone Library. J. Combi. Chem. 6, 478-486, 2004.
Yan, B., Collins, N., Wheatley, J., Irving, M., Leopold, K., Chan, C., Shornikov, A., Fang, L., Lee, A., Stock, M., Zhao, J. High-Throughput Purification of Combinatorial Libraries I: A High-Throughput Purification System Using an Accelerated Retention Window Approach. J. Combi. Chem. 6, 255-261, 2004.
Fang, L., Zhao, J., Yan, B. High throughput parallel LC/UV/MS analysis of combinatorial libraries in Methods in Enzymology, Volume 369, Pages 3-21. Combinatorial Chemistry, Part B. Edited by: Guillermo A. Morales and Barry A. Bunin, 2004.
Yan, B., Fang, L., Irving, M., Zhang, S., Boldi, A. M., Woolard, F., Johnson, C. R., Kshirsagar, T., Figliozzi, G. M., Krueger, A. C., Collins, N., Quality Control in Combinatorial Chemistry: Determination of the Quantity, Purity, and Quantitative Purity of Compounds in Combinatorial Libraries. J. Combi. Chem. 5(5), 547-559, 2003.
Fang, L., Demee, M., Cournoyer, J., Sierra, T., Young, C., Yan, B. Parallel high-throughput accurate mass measurement using a nine-channel multiplexed electrospray LC/UV/TOFMS system. Rapid Commun. Mass Spectr. 17, 1425-1432, 2003.