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Roman Manetsch

Roman Manetsch

Roman Manetsch
Associate Professor

Contact

Office: NES 331A
Phone: 813/974-7306
Email:

Links

Education

Diploma in Chemistry, University of Basel (Switzerland), 1998
Ph.D., University of Basel (Switzerland), 2002
Postdoctoral Fellow, The Scripps Research Institute (La Jolla, CA), 2002-2005

Research

The Manetsch laboratory is focusing on research in organic chemistry and chemical biology addressing in particular modern aspects of medicinal chemistry. The conducted research includes the development of new drug/target discovery methods, hit-to-lead optimization, the design and synthesis of new biochemical tools, as well as their application to biologically relevant processes.

One of the research interests in the group is the discovery and investigation of biologically relevant receptors. Investigation of protein-ligand or receptor-ligand interactions remains an inexhaustible challenge for chemistry and biology. Today researchers face the impressive challenge of assigning molecular and cellular function to the tremendous number of protein-ligand or receptor-ligand interactions. The goal of this projects is to develop new tools for the selective labeling of protein targets in complex mixtures.

Protein-protein interactions are central to many biological processes, and they represent a large and important class of targets for human therapeutics. However, modulating protein-protein interactions with small, drug-like molecules is, in general, extremely difficult due to issues such as the lack of well-defined binding pockets on the protein surfaces. Currently, there are no general techniques or approaches for the development of potent and effective protein-protein interaction modulators (PPIMs). The Manetsch laboratory focuses on the development of a reliable strategy for the discovery and development of PPIMs. This strategy relies on a kinetic target-guided synthesis (TGS) approach, which uses the target protein to synthesize a bidentate ligand by equilibrium-controlled sampling of fragments carrying complementary reactive functionalities until an irreversible reaction connects the pair of fragments that best fits the protein's binding pockets. This searching process ends when two fragments irreversibly form a bidentate molecule, thereby locking in information about the target protein which recruited them.

Hit-to-lead optimization is another focus of the Manetsch laboratory. Using modern approaches including structure-activity and structure-property relationship studies, compounds are developed, which show in vivo activity. The Manetsch laboratory is especially interested in hit-to-lead optimization for the development of biologically active for neglected diseases such as malaria and leishmaniasis.

Current Funding

View our currently funded projects here.

Postdoctoral Associates

Dr. Niranjan Namelikonda

Graduate Students

Iredia Iyamu, Sameer Kulkarni, Arun Babu Kumar, Cynthia Lichorowic, Jordany Maignan, Andrii Monastyrskyi, Katja Nacheva, Kurt Van Horn

Recent Publications

  1. Nacheva K P, Maza W, Mayer D Z, Fronczek F, Larsen R W, Manetsch R*. Fluorescent Properties and Resonance Energy Transfer of 3,4-bis(2,4-difluorophenyl)-maleimide. Submitted.
  2. Kumar A B, Anderson J M, Melendez A L, Manetsch R*. Synthesis and structure-activity relationship studies of 1,3-disubstituted 2-propanols as BACE-1 inhibitors. Submitted.
  3. Namelikonda N K, Manetsch R*. Sulfo-click reaction via in situ generated thioacids and its application in kinetic target-guided synthesis. Chem Commun 2012; 48, 1526-1528.
    Article has been published in the "Emerging Investigators 2012" issue.
  4. Cross R M, Namelikonda N K, Mutka T S, Luong L, Kyle D E, Manetsch R*. Synthesis, Antimalarial Activity, and Structure–Activity Relationship of 7-(2-Phenoxyethoxy)-4(1H)-quinolones. J Med Chem 2011; 54, 8321-8327.
  5. Kumar A B, Anderson J, Manetsch, R*. Design, Synthesis and Photoactivation Studies of Fluorous Photolabels. Org Biomol Chem 2011; 9, 6284-6292.
  6. Kulkarni S S, Hu X-D, Doi K, Wang H-G, Manetsch R*. Screening of Protein-Protein Interaction Modulators via Sulfo-Click Kinetic Target-Guided Synthesis. ACS Chemical Biology 2011; 6, 724-732.
    Appeared in the list of 20 "most read" ACS Chemical Biology articles in 2011.
  7. Cross M R, Maignan J R, Mutka T S, Luong L, Sargent J, Kyle D K, Manetsch R*. Optimization of 1,2,3,4-Tetrahydroacridin-9(10H)-ones as Antimalarials Utilizing Structure-Activity and Structure-Property Relationships. J Med Chem 2011; 54, 4399-4426.
  8. Cross R M, Manetsch R*. Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings. J Org Chem 2010; 75, 8654-8657.
  9. Cross M R, Monastyrskyi A, Mutka T S, Burrows J, Kyle D K, Manetsch R*. Endochin Optimization: Structure-Activity and Structure-Property Relationship Studies of 3-substituted 2-Methyl-3(1H)-quinolones with Antimalarial Activity. J Med Chem 2010; 53, 7076-7094.
  10. Hu. X. Manetsch R*. Kinetic Target-Guided Synthesis. Chem Soc Rev 2010, 39, 1316-1324.
  11. Radic Z, Manetsch R, Fournier D, Sharpless KB, Taylor P*. Probing Gorge Dimensions of Cholinesterases by Freeze-Frame Click Chemistry. Chem-Biol Interact 2008; 175: 161-165.
  12. Hu X, Sun J, Wang H-G, Manetsch R*. Bcl-XL-Templated Assembly of its Own Protein-Protein Interaction Modulator from Fragments Decorated with Thio Acids and Sulfonyl Azides. J Am Chem Soc 2008; 130: 13820-13821.
  13. Sharpless KB, Manetsch R*. In Situ Click Chemistry: A Powerful Means for Lead Discovery (Review). Expert Opinion on Drug Discovery 2006; 1: 525-538.