Directory: Faculty

Haitao (Mark) Ji ORGANIC & BIOORGANIC CHEMISTRY Assistant Professor B.S., Second Military Medical University, China, 1994 Ph.D., Second Military Medical University, China, 1999 Postdoctoral fellow, Northwestern University, 2002-2006 Research Associate Professor, Northwestern University, 2007-2010 Phone: (801) 581-6747 Office: 4428 HEB-S Email: markji@chem.utah.edu Research Group Biological Chemistry Program Publications

Activities & Awards

• First Prize for Scientific and Technological Progress Award, conferred by the Chinese People’s Liberation Army, 2002
• Servier National Young Investigator Award in Medicinal Chemistry of China, 1999

Research Interests

Research interests in our laboratory lie at the interface of chemistry and biology. We mainly focus on structure-based design and synthesis of “smart” small molecules that can modulate cellular signaling pathways with an emphasis on protein-protein interactions and target specificity. Technique cores in our laboratory are fragment-based screening and de novo design, the design and synthesis of versatile fragment building blocks from natural products, and construction of fragment libraries to explore isozyme selectivity.

Specific areas of interest include: (1) Fragment-based design of novel small-molecules to selectively disrupt key interactions in the Wnt/beta-catenin signaling pathway; (2) Development of new organic chemistry-oriented techniques to differentiate drug target cytochrome P450s from drug-metabolizing P450s, and the design and synthesis of selective inhibitors for drug target P450s; (3) Incorporation of natural product building blocks into peptides to mimic their biological functions. Our long-term goal of this study is the systematic data mining of natural product building blocks and the study of their ability as versatile building blocks for fragment-based inhibitor design. We take multidisciplinary approaches toward achieving these research goals including synthetic organic chemistry, computer modeling, molecular and cell biology.

Selected Publications

• Ji, H.; Delker, S. L.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives. J. Med. Chem. 2010, Submitted.
• Delker, S. L.; Ji, H.; Li, H.; Jamal, J.; Fang, J.; Xue, F.; Silverman, R. B.; Poulos, T. L. Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of a cerebral palsy phenotype in an animal model. J. Am. Chem. Soc. 2010, 132(15), 5437-5442.
• Ji, H.; Tan, S.; Igarashi, J.; Li, H.; Derrick, M.; Martásek, P.; Roman, L. J.; Vásquez-Vivar, J.; Poulos, T. L.; Silverman, R. B. Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy. Ann. Neurol. 2009, 65(2), 209-217.
• Ji, H.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping. J. Med. Chem. 2009, 52(3), 779-797.
• Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors. J. Am. Chem. Soc. 2008, 130(12), 3900-3914.
• Ji, H.; Gómez-Vidal, J. A.; Martásek, P.; Roman, L. J.; Silverman, R. B. Conformationally restricted dipeptide amides as potent and selective neuronal nitric oxide synthase inhibitors. J. Med. Chem. 2006, 49(21), 6254-6263.
• Ji, H.; Li, H.; Flinspach, M.; Poulos, T. L.; Silverman, R. B. Computer modeling of selective regions in the active site of nitric oxide synthases: implication for the design of isoform-selective inhibitors. J. Med. Chem. 2003, 46(26), 5700-5711.
• Ji, H.; Zhang, W.; Zhang, M.; Kudo, M.; Aoyama, Y.; Yoshida, Y.; Sheng, C.; Song, Y.; Yang, S.; Zhou, Y.; Lü, J.; Zhu, J. Structure-based de novo design, synthesis and biological evaluation of nonazole inhibitors specific for lanosterol 14alpha-demethylase of fungi. J. Med. Chem. 2003, 46(4), 474-485.
• Ji, H.; Zhang, W.; Zhou, Y.; Zhang, M.; Zhu, J.; Song, Y.; Lü, J.; Zhu J. A three-dimensional model of lanosterol 14a-demethylase of Candida albicans and its interaction with azole antifungals. J. Med. Chem. 2000, 43(13), 2493-2505.