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제 목 : High-affinity and controllable host-guest chemistry as a new supramolecular tool for biology and biomedicine
연 사 : 박경민 박사(IBS)
일 시 : 2020년 10월 15일(목) 오후 4시 30분
-미팅룸 번호 : 571 508 642
High-affinity and controllable host-guest chemistry as a new supramolecular tool for biology and biomedicine
Kyeng Min Park
Center for Self-assembly and Complexity (CSC), Institute for Basic Science (IBS),
Pohang 37673, Republic of Korea
Due to a high binding affinity (Ka ~ 1013 M-1), the streptavidin (Sv) and biotin (BT) as a protein-ligand binding pair has been utilized as a useful tool for various bioapplications including protein imaging and identification. However, the Sv-BT pair has some intrinsic shortcomings; 1) interference of binding from endogenous biotins, 2) false positive signals caused by endogenously biotinylated proteins 3) difficulty in chemical modification and instability of streptavidin (protein) degraded by proteases in cellular conditions. Recently, we developed a new ultrastable and controllable synthetic binding pair as “supramolecular latching system” consisting of a pumpkin-shaped synthetic host molecule, cucurbituril (CB) and adamantylamine (AdA), which has almost comparable (or even higher) binding affinity (Ka ~1012-15 M-1) to Sv-BT with unique features including 1) bio-orthogonality in binding which does not affected by endogenous biomolecules such as biotin, 2) small size with stable and robust chemical structure, 3) scalability using known chemical synthetic methods and 4) controllable binding affinity by treating strong competitors. In this talk, I will introduce our recent efforts to develop this supramolecular latching system as a new molecular tool for various bioapplications (Fig. 1) including visualization and identification of spatial proteins in cells and cost-effective purification of therapeutic proteins in high purity. In addition, future direction of research and development of this new molecular tool will be discussed.
Figure 1. Schematic illustration of “supramolecular latching system” and its bioapplications
1. An, J.; Kim, S.; Shrinidhi, A.; Kim, J.; Banna, H.; Sung, G.; Park, K. M.* M.*; Kim, K* “Purification of protein
therapeutics via high aff inity supramolecular host guest interactions” Nat. Biomed. Eng. 2020 , in press.
(DOI:10.1038/s41551 020 0589 7).
2. Ghosh; S. K.; Dhamija, A.; Ko, Y. H.; An, J.; Hur, M. Y.; Boraste, D. R.; Seo, J.; Lee, E.*; Park, K. M.*
Kim, K.* Superacid mediated functio nalization of hydroxylated cucurbit[ n ]urils J. Am. Chem. Soc. 2019 ,
3. Kim, K. L.; Sung, G..; Sim, J.; Murray, J.; Li, M.; Lee, A.; Shrinidhi, A.; Park, K. M. M.*; Kim, K.*
“Supramolecular latching system based on ultrastable synthetic binding pair s as versatile tools for protein
imaging” Nat. Commun. 2018 , 9, 1712.
4. Li, M.; Lee, A.; Kim, K. L.; Murray, J.; Shrnidhi, A.; Sung, G.; Park, K. M. M.*; Kim, K.* “Autophagy caught
in the act: a supramolecular FRET Pair based on an ultrastable synthetic Host g uest complex visualizes
autophagosome lysosome fusion.” Angew. Chem. Int. Ed. 2018, 57 ,
5. Park, K. M. M.*; Baek, K.; Ko, Y. H.; Shrinidhi, A.; Murray; Jang, W. H.; Kim, K. H.; Lee, S., Yoo, J.; Kim,
S.; Kim, K.* “Mono allyloxylated cucurbituril acts as an unconventional amphiphile to form
light responsive vesicles” Angew. Chem. Int. Ed. 2018 , 57, 3132