Office: CHE 202d
B.A., University of South Florida
Ph.D., University of South Florida
Postdoctoral Associate, Duke University
Sr. Postdoctoral Associate, Columbia University
Dr. Guida's research is focused on computer aided drug design. An area of specific interest to the Guida Lab is the design of inhibitors of enzymes essential for the biosynthesis of polyamines, which are critical for the replication of DNA and are elevated in a number of human tumors. This work has focused on the design of S-adenosylmethionine decarboxylase inhibitors as potential anti-cancer agents and involves a collaboration with Professor Steve Ealick (Cornell University), Professors Anthony Pegg and Diane McCloskey (Hershey Medical Center at Penn State University) and Drs. Jack Secrist and Bill Waud (Southern Research Institute). Through collaboration with investigators at the Moffitt Cancer Center & Research Institute, Dr. Guida has also been involved in the computational design of inhibitors of other enzymes and inhibitors of protein-protein interactions that have therapeutic relevance in cancer. This work includes the following biomolecular targets: farnesyl transferase and geranylgeranyl transferase (in collaboration with Drs. Said Sebti and Nick Lawrence), the 20S Proteasome (with Drs. Said Sebti and Mark McLaughlin), MDM2-p53 and MDMX-p53 (with Drs. Jian-dong Chen and Mark McLaughlin) and Shp2 (with Drs. Jerry Wu and Nick Lawrence). Dr. Guida's lab has also been interested in developing enhanced methods for the docking of inhibitors into protein binding sites in which induced fit effects are important and in applying computational techniques to the problem of elucidating the mechanistic details of enzyme catalysis. Dr. Guida also has an interest in the design, synthesis, and study of model complexes that mimic zinc metalloproteases.
View our currently funded projects here.
Back Row: Divya, Courtney and Dan; Front Row Sai, Katherine and Jacob Weismann
- “Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors” Lawrence H.R.; Kazi, A.; Luo, Y.; Kendig, R.; Ge, Y.; Jain, S.; Daniel, K.; Santiago, D.; Guida, W.C.; Sebti, S.M. Bioorg. Med. Chem. 2010, 18, 5576.
- “Facile iterative synthesis of 2,5-terpyrimidinylenes as nonpeptidic alpha-helical mimics” Anderson, L.; Zhou, M.; Sharma, V.; McLaughlin, J.M.; Santiago, D.N.; Fronczek, F.R.; Guida, W.C.; McLaughlin, M.L. J. Org. Chem., 2010, 75, 4288.
- “Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112” Chen, L; Pernazza, D.; Scott, L.M.; Lawrence, H.R.; Ren, Y.; Luo, Y.; Wu, X.; Sung, S-S.; Guida, W.C.; Sebti, S.M.; Lawrence, N.J.; Wu. J. Biochem Pharmacol., 2010, 80, 801.
- “Role of the sulfonium center in determining the ligand specificity of human S-adenosylmethionine decarboxylase” Bale, S.; Brooks, W.; Hanes, J.W.; Mahesan, A.M.; Guida, W.C.; Ealick, S.E. Biochemistry, 2009, 48, 6423.
- “Discovery of a novel proteasome inhibitor selective for cancer cells over non-transformed cells” Kazi, A.; Lawrence, H.; Guida, W.C.; McLaughlin, M.L.; Springett, G.M.; Berndt, N.; Yip, R.M.; Sebti, S.M.; Cell Cycle, 2009, 8,1940.
- “Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking” Lawrence, H.R.; Li Z.; Yip, M.L.; Sung, S-S.; Lawrence, N.J.; McLaughlin, M.L; McManus, G.J.; Zaworotko, M.J.; Sebti, S.M.; Chen, J.; Guida, W.C. Bioorg Med Chem Lett., 2009,19, 3756.
- “New Insights into the Design of Inhibitors of Human S-Adenosylmethionine Decarboxylase: Studies of Adenine C(8) Substitution in Structural Analogues of S-Adenosylmethionine”, McCloskey, D.E.; Bale, S.; Secrist, J.A.; Tiwari, A.; Moss, T.H.; Valiyaveettil, J.; Brooks, W.H.; Guida, W.C.; Pegg, A.E.; Ealick, S.E. J Med. Chem., 2009, 51, 7144.
- “Substitution of Aminomethyl at the Meta-Position Enhances the Inactivation of O(6)-Alkylguanine-DNA Alkyltransferase by O(6)-Benzylguanine.”, Pauly, G. T.; Loktionova, N. A.; Fang, Q.; Vankayala, S. L.; Guida W. C.; Pegg, A. E. J. Med. Chem., 2008, 51, 7144.
- “Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds”, Lawrence, H.R.; Pireddu R.; Chen, L.; Luo, Y; Sung, S-S; Szymanski, A.M.; Yip, M.L.; Guida W. C.; Sebti, S.M.; Wu, J; Lawrence, N.J. J. Med. Chem., 2008, 51, 4948.
- “A small-molecule E2F inhibitor blocks growth in a melanoma culture model”, Ma, Y.; Kurtyka, C. A.; Boyapalle, S.; Sung, S-S; Lawrence, H.; Guida, W.; Cress, W.D.; Cancer Res., 2008, 68, 6292.
- “Computational validation of the importance of absolute stereochemistry in virtual screening", Brooks, W.H.; Daniel, K.G.;Sung, S-S; Guida, W.C. J Chem. Inf. Model., 2008, 48, 639.
- “In Silico Chemical Library Screening and Experimental Validation of a Novel 9-Aminoacridine Based Lead-Inhibitor of Human S-Adenosylmethionine Decarboxylase”, Brooks, W.H.; McCloskey, D.E.; Daniel, K.G.; Ealick, S.E., Secrist, J.A.3rd, Waud, W.R.; Pegg, A.E.; Guida, W.C. J. Chem. Inf. Model. 2007, 47,1897.
- “Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity”, Siddiquee, K.; Zhang, S.; Guida, W. C.; Blaskovich, M. A.; Greedy, B.; Lawrence, H. R.; Yip, M. L.; Jove, R.; McLaughlin, M. M.; Lawrence, N. J.; Sebti, S. M.; Turkson, J. Proc. Natl. Acad. Sci. USA 2007, 104, 7391.