Research Interest of Sangsoo Kim

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Background

I have started my research career in the area of X-ray crystallography when I was a M.S. candidate at the Dept. of chemistry, Seoul National University, under the guidance of Prof. Whanchul Shin.  My Ph.D. course at the Dept. of chemistry, Iowa State University under the guidance of Prof. R.A. Jacobson, was more focused on crystallography itself, developing novel methods for structure solution as well as writing appropriate programs.  Of course, I applied the methods I developed to solve several structures, including a powder diffraction method applied to Bi-doped lead dioxide surfaces in collaboration with Prof. In Hyung Yeo.

During my postdoctoral work, I moved on to bio-molecular crystallography, especially virus crystal structure determination.  Prof. M.G. Rossmann's lab at the Dept. of Biol. Sci., Purdue University, was the pioneer at solving picorna virus structures.  I was involved the structural studies of HRV-1A and Mengo viruses.  We were also active at solving inhibitor complex structures in order to understand structural basis of some of the antiviral drugs Sterling-Winthrop was developing at the time.  It was a pioneering work of rational drug design that is called now structure-based drug design. 

By the time I was about to finish my postdoctoral work, Prof. Janet Smith informed us that Merck solved HIV-1 protease structure.  I did not understand its importance until I was working on the development of HIV-1 protease inhibitors at LG Biotech Research Institute.  For the first couple of years at LG, I was involved in protein engineering focusing on developing mutant protein sweetner, Monellin.  It was notorious of having late on-set and lingering effect.  We hoped to ameliorate these unwanted effect through site-directed mutation.  Actually we were tasting by ourselves!  Improving thermostability was another interest to be used as a sugar-substitute in coffee.  I also solved the crystal structure of the single-chain recombinant monellin.

Discussion with Sung Chun Kim led me back to structure-based drug design field.  We were interested in HIV-1 protease as the apo and inhibitor complex strucures were available on PDB.  Sung Chun, as an enzymologist, came up with an epoxide-based irreversible inhibition.  We pilot-tested the concept with carboxypeptidase A with an inhibitor developed by Prof. D. Kim at POSTECH.  It was published in JACS and fascinated us with epoxide.  I designed a cis-epoxide against HIV-1 protease and it was a success as 116th compound went to clinical trial.

Encouraged by this success, I launced oral thrombin inhibitor program with Youngsoo Oh, my classmate at SNU.  I used bovine thrombin structures complexed with various inhibitors and came up with benzamidrazone series that had high selectivity to thrombin and orally bioavailable.  Behold, the 57th compound was selected as the clinical candidate and licensed to Parke-Davis, then and now, Pfizer.

Since then, I witnessed launching of several new drug development programs but all of them are well-known targets.  I thought that it is boring to design drug based on structure.  I thought it could be a routine job, automatable some day.  I found more excitement in genomics and bioinformatics that were chasing after novel targets.  That's how I've gotten into bioinformatics.