[Á÷¹«¼³¸í ¿ä¾à]
´ë»ç½Å¾àÆÀ¿¡¼´Â Â÷¼¼´ë ´ë»çÁúȯ Ä¡·áÁ¦ °³¹ßÀ» ÁÖµµÇÒ ´Ü¹éÁú ±¸Á¶ºÐ¼®(±¸Á¶±Ô¸í) ¿¬±¸¿øÀ» ¸ðÁýÇÕ´Ï´Ù.
½Å±Ô ´ë»çÁúȯ Ä¡·áÁ¦ °³¹ßÀ» À§ÇÑ ½Å±ÔŸ°Ù´Ü¹éÁúÀÇ ´Ü¹éÁú ¹ßÇö/Á¤Á¦ ¹× ±¸Á¶ ±Ô¸í(X-ray crystallography, cryo-EM) ¿¬±¸¸¦ ÁøÇàÇÏ¿©,
hit-to-lead ÃÖÀûÈ ´Ü°è±îÁö ±¸Á¶±â¹Ý¾à¹°°³¹ß(SBDD)À» ¼öÇàÇϸç,
À̸¦ ÅëÇØ °æÀï·Â ÀÖ´Â ÀÓ»ó Èĺ¸¹°ÁúÀ» ¹ß±¼ ¹× ±Û·Î¹ú ÁøÃâ¿¡ ±â¿© ÇÕ´Ï´Ù.
[Á÷¹« ¼³¸í]
1. ´Ü¹éÁú ¹ßÇö ¹× Á¤Á¦
- Target ´Ü¹éÁú µðÀÚÀÎ, À¯ÀüÀÚ Å¬·Î´× ¹× ¹ßÇö º¤ÅÍ ±¸Ãà
- ´Ù¾çÇÑ ¹ßÇö ½Ã½ºÅÛ(´ëÀå±Õ, °ïÃæ¼¼Æ÷, Æ÷À¯µ¿¹°¼¼Æ÷ µî)À» ÀÌ¿ëÇÑ ÀçÁ¶ÇÕ ´Ü¹éÁú ¹ßÇö
- ´Ü¹éÁú ¹ßÇö Á¶°Ç ÃÖÀûÈ ¹× ´ë·® »ý»ê °øÁ¤ °³¹ß
- Ä£È Å©·Î¸¶Åä±×·¡ÇÇ(Affinity chromatography), À̿±³È¯ Å©·Î¸¶Åä±×·¡ÇÇ(Ion-exchange chromatography), Å©±â ¹èÁ¦ Å©·Î¸¶Åä±×·¡ÇÇ(Size-exclusion chromatography) µî ´Ù¾çÇÑ ±â¹ýÀ» Ȱ¿ëÇÑ °í¼øµµ ´Ü¹éÁú Á¤Á¦
- Á¤Á¦µÈ ´Ü¹éÁúÀÇ Ç°Áú °ü¸® (SDS-PAGE, DLS, Western blot µî)
2.´Ü¹éÁú ±¸Á¶ºÐ¼® (X-ray crystallography, cryo-EM)
- ´Ü¹éÁú °áÁ¤È (Crystallization) Á¶°Ç ½ºÅ©¸®´× ¹× ÃÖÀûÈ ¼öÇà
- X-ray ȸÀý µ¥ÀÌÅÍ ¼öÁý, ó¸® ¹× ºÐ¼®
- Cryo-EMÀ» Ȱ¿ëÇÑ ±¸Á¶ ºÐ¼® ¿ª·®
- ´Ü¹éÁú 3Â÷¿ø ±¸Á¶ ±Ô¸í ¹× ±¸Á¶ ±â¹Ý ºÐ¼® (Structure-based analysis)
3. ´Ü¹éÁú °áÇÕ·Â ºÐ¼® (SPR, TSA, ITC µî)
- SPR (Surface Plasmon Resonance) ±â¹Ý ´Ü¹éÁú-¸®°£µå °£ °áÇÕ Ä£Èµµ(Affinity) ¹× °áÇÕ µ¿¿ªÇÐ(Kinetics) ºÐ¼®
- TSA (Thermal Shift Assay)¸¦ ÀÌ¿ëÇÑ ´Ü¹éÁú ¾ÈÁ¤¼º ¹× ¸®°£µå °áÇÕ È®ÀÎ
- ºÐ¼® °á°ú µ¥ÀÌÅÍ ÇØ¼® ¹× º¸°í¼ ÀÛ¼º
[ ÇÙ½É ¿ª·® ¹× ±â¼ú ]
1. ¸·´Ü¹éÁú(GPCR) ´Ü¹éÁú ¹ßÇö/Á¤Á¦ ´É·Â
2. ´Ü¹éÁú-ÈÇÕ¹° °áÁ¤È ´É·Â.
3. Binsding affinity Æò°¡ ¹× ºÐ¼® ´É·Â
[ °æÇè°ú Áö½Ä ]
1. °ü·Ã ¿¬±¸ºÐ¾ß ¼®»çÇÐÀ§ ÀÌ»ó Ãëµæ
2. Á¦¾àȸ»ç/¿¬±¸¼Ò °ü·Ã ¿¬±¸ °æ·Â
[Àü¹® ºÐ¾ß/ÀÚ°Ý¿ä°Ç]
1. ¼®»ç ÇÐÀ§ Ãëµæ ÈÄ ½Å¾à¿¬±¸°³¹ß °æ·Â 3³â ÀÌ»ó ¶Ç´Â ÀÌ¿¡ »óÀÀÇÏ´Â °æ·Â º¸À¯
2. ´Ü¹éÁú ±¸Á¶ ºÐ¼® Àü°øÀÚ
3. ´Ü¹éÁú ¹ßÇö ¹× Á¤Á¦ ¿ª·® º¸À¯
4. Binding affinity ºÐ¼® (TSA, SPR, ITC µî)
[¿ì´ë»çÇ×]
1. ½Å¾à¿¬±¸°³¹ß °ü·Ã °æÇèÀÚ
2. »ý¸í°úÇÐ/±¸Á¶»ý¹°ÇÐ Àü°øÀÚ
3. ¿µ¾î ´ÉÅëÀÚ
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