Project/Area Number |
22KJ1165
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Project/Area Number (Other) |
22J23271 (2022)
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Research Category |
Grant-in-Aid for JSPS Fellows
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Allocation Type | Multi-year Fund (2023) Single-year Grants (2022) |
Section | 国内 |
Review Section |
Basic Section 34010:Inorganic/coordination chemistry-related
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Research Institution | The University of Tokyo |
Principal Investigator |
YUAN WEI 東京大学, 工学系研究科, 特別研究員(DC1)
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Project Period (FY) |
2023-03-08 – 2025-03-31
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Project Status |
Granted (Fiscal Year 2023)
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Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2024: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2023: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2022: ¥900,000 (Direct Cost: ¥900,000)
|
Keywords | peptide helix / dynamic helix / high pressure / Peptide Helix / Peptide Dynamics |
Outline of Research at the Start |
The main goal of my project is to develop a MOF that allows helical inversion of dynamic peptides in the crystalline state. To achieve this goal, the main strategy is to use achiral Aib-rich peptides as helical pillar ligands to construct pillared-layer MOFs.
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Outline of Annual Research Achievements |
Helix is a common structural motif that can exist across spatial scales, from an electron spin, a peptide helix to a DNA duplex. The dynamic behaivors of helix play a crucial role in various events, such as cell signal transduction. The dynamic property of helix is widely studied in solution state, while I achieved the dynamic motion of helix in the crystalline state, where molecular motion is largely restricted. The crystal is known as AibMOF. The peptides in the framework are spaced apart by specific distances to allow for dynamic movement. Through NMR spectroscopy, I was able to observe the dynamic helix inversion of peptides within the peptide framework. Furthermore, by applying pressure to the framework, I could control the movement of the peptides.
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
I have gathered sufficient data to characterize the dynamic helix inversion in the AibMOF system. The solid state NMR spectra clearly indicate that the signals associated with the P- and M-helical structures coalesce and split reversibly as a functional of temperature, indicating that the helices are dynamically inverting in the crystalline state. Moreover, I was able to manipulate the helical inversion dynamics by applying hydrostatic pressure to the framework using a diamond anvil cell. Upon certain pressure, the helical inversion motion stopped, and the peptides exhibited an ordered arrangement with alternating P- and M-helices. This was confirmed by high pressure single crystal X-ray diffraction analysis.
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Strategy for Future Research Activity |
One interesting feature of dynamic helices is the possibility to bias the helices into homochirality. When AibMOF accommodates a chiral guest, the frameworks potentially recognize and memorize the chiral information by biasing the helical handedness. To control the helical screw-sense, MOF crystals are immersed in enantiopure liquids (2-butanol, limonene, etc.). Due to the intrinsic porosity, the MOF crystals can incorporate chiral molecules as guests. With a possible interaction with chiral guest molecules, the Aib pillars are expected to keep a handedness preference. Moreover, we have a chance to rewrite the helicity upon guest exchange.
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