| Info. | Vol.1 - No.1 (2007.03.20) |
|---|---|
| Title | Desorption/Ionization on Mesoporous silicate (DIOM)-Mass Spectrometry (MS) and Ultrafiltration for Target-based Drug Screening |
| Authors | Chang-Soo Lee1, Hwan-Moon Song1, Kyoung-Ku Kang2, Chang-Hyoung Choi1, Hyun-Ku Rhee3 & Byung-Gee Kim3 |
| Institutions | 1Department of Chemical and Biological Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764, Korea 2Electronic Chemical Materials R&D Center, Research Institute of Chemical & Electronic Materials, Samsung Cheil Industry, Inc., Kyeonggi-do 437-711, Korea 3School of Chemical and Biological Engineering, Seoul National University, Kwanak-gu, Seoul 151-742, Korea Correspondence and requests for materials should be addressed to C.S. Lee (rhadum@cnu.ac.kr) |
| Abstract | This study presents a novel approach for rapid screening of combinatorial libraries to identify binding molecules for target proteins. Ultrafiltration coupled with desorption/ionization on mesoporous silicate (DIOM)-mass spectrometry (MS) provides a rapid, simple but powerful approach for the preliminary screening of active ligands toward specific target receptors. The feasibility of this strategy is demonstrated with a library of small molecule ligands (11 compounds) and the target protein, human serum albumin (HSA). Equimolar mixture of library was incubated with HSA under native binding conditions. Subsequently, the high molecular weight protein-drug complexes were selectively compartmented by ultrafiltration. The bound small molecular weight drugs were released and then recovered by denaturation of HSA for analysis by DIOM-MS. DIOM-MS directly provided clean mass spectra of binding compounds without any interference below 300 Da. This simple and robust method can preliminarily screen various chemical entities from a combinatorial mixture to find compounds with strong binding affinity (above 1.0횞103 M-1) toward the target protein. |
| Keyword | DIOM-MS, Ultrafiltration, Drug screening, HSA |
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