Hyun-Suk Lim, Ph.D.
Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
John D. Van Nuys Medical Science Building
635 Barnhill Drive, Room 4053
Indianapolis, Indiana 46202-5126
Phone: (317) 274-7151
Facsimile: (317) 274-4686
Ph.D., 2004, POSTECH, Pohang, Korea
Postdoctoral Fellow, 2005-2008, University of Texas Southwestern Medical Center, Dallas, TX
Area of Study
Chemical biology and drug discovery: identification of small molecules that modulate cellular signaling pathways with an emphasis on protein-protein interactions for use as biological probes and therapeutic agents. More details...
Selected Recent Publications
Lee, J. H.; Lim, H. S. "'Solid-phase synthesis of tetrasubstituted pyrrolo[2,3-d]pyrimidines." Org. Biomol. Chem. 2012, in press.
Lee, J. H.; Kim, H. S.; Lim, H. S. "Design and facile solid-phase synthesis of conformationally constrained bicyclic peptoids." Org. Lett. 2011, 13, 5012-5015. (Recommended in Faculty of 1000 Biology).
Nelson-Mendez, A.; Aleksanian, S.; Oh, M.; Lim, H. S.; Oh, J. K. “Reductively-degradable polyester-based block copolymers prepared by facile polycondensation and ATRP: synthesis, degradation, and aqueous micellization.” Soft Matter. 2011, 7, 7441-7452.
Lee, J. H.; Zhang, Q.; Jo, S.; Chai, S. C.; Oh, M.; Im, W.; Lu, H.; Lim, H. S. "Novel pyrrolopyrimidine-based α-helix mimetics: cell permeable inhibitors of protein-protein interactions." J. Am. Chem. Soc. 2011, 133, 676-679(Recommended in Faculty of 1000 Biology; Highlighted in SciBX: Science-Business eXchange, 2011, 4(3)).
Lee, J. H.; Meyer, A. M.; Lim, H. S. “A simple strategy for the construction of combinatorial cyclic peptoid libraries.” Chem. Commun. 2010, 46, 8615-8617.
Lee, J.; Udugamasooriya, G.; Lim, H. S.; Kodadek, T. “Potent and selective photo-inactivation of proteins with peptoid-ruthenium conjugates.” Nature Chem. Biol. 2010, 6, 258-260 (Recommended in Faculty of 1000 Biology).
Kim, Y. C.; Wu, S. Y.; Lim, H. S.; Chiang, C. M.; Kodadek, T. “Non-proteolytic regulation of p53-mediated transcription through destabilization of the activator-promoter complex by the proteasomal ATPases.” J. Biol. Chem. 2009, 285, 34522-34530.
Lim, H. S.; Reddy, M. M.; Xiao, X.; Wilson, J.; Wilson, R.; Connell, S.; Kodadek, T. “Rapid identification of improved protein ligands using peptoid microarrays.” Bioorg. Med. Chem. Lett. 2009, 19, 3866-3869 (Invited for symposium-in-print issue in honor of Professor Carlos F. Barbas for his Tetrahedron Young Investigator Award).
Lim, H. S.; Archer, T. C.; Kim, Y. C.; Hutchens, T.; Kodadek, T. “Rapid identification of the pharmacophore in a large peptoid inhibitor of the proteasome regulatory particle.” Chem. Commun. 2008, 1064-1066 (Featured at Chemical Biology of Royal Society of Chemistry Publishing, 2008, 3; highlighted in NewsSpots (NHLBI Proteomics), Winter 2008).
Lim, H. S.; Cai, D.; Archer, T. C.; Kodadek, T. “Periodate-triggered cross-linking reveals Sug2/Rpt4 as the molecular target of a peptoid inhibitor of the 19S proteasome regulatory particle.” J. Am. Chem. Soc. 2007, 129, 12936-12937.
Lim, H. S.; Archer, T. C.; Kodadek, T. “Identification of a peptoid inhibitor of the proteasome regulatory particle.” J. Am. Chem. Soc. 2007, 129, 7750-7751. (Recommended in Faculty of 1000 Biology; highlighted in NewsSpots (NHLBI Proteomics), 2007, Fall, 2).
Xiao, X.; Yu, P.; Lim, H. S.; Sikder, D.; Kodadek, T. “Design and synthesis of a cell permeable synthetic transcription factor mimic.” J. Comb. Chem. 2007, 9, 592-600 (Selected as most-cited articles published in 2007).
Xiao, X.; Yu, P.; Lim, H. S.; Sikder, D.; Kodadek, T. “A cell permeable synthetic transcription factor mimic.” Angew. Chem. Int. Ed. 2007, 46, 2865-2868 (Featured in Nature 2007, 446, 472).
Research interests in my laboratory lie at the interface of chemistry and biology. Our goal is to discover and develop novel molecular entities that modulate cellular signaling pathways with an emphasis on protein-protein interactions. To this end, we take a multidisciplinary approach including synthetic organic chemistry, combinatorial chemistry, medicinal chemistry, molecular biology and cell biology.
Protein-protein interactions play pivotal roles in virtually every biological process and thus are emerging as promising therapeutic targets for various diseases including cancer. However, most such interactions cannot be readily disrupted by small molecules, since protein-protein interaction sites are fairly large and shallow. To identify molecules that disrupt protein-protein interactions, we focus on the design and construction of small molecule or peptidomimetic libraries that can mimic protein secondary structures or target a compact region of protein-protein interaction, so called "hot spot", high-throughput screening of the libraries (using either forward or reverse chemical genetic approach), and functional characterization of the identified compounds. Selected lead compounds will be further elaborated structurally based on structural information such as X-ray and NMR studies to improve their potency and specificity, and evaluated functionally in vivo in collaboration with other research groups. The resulting compounds will serve as highly useful biological probes to elucidate the functions of target proteins in model systems. They may also have potential as novel therapeutic candidates.