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Structure-Guided Designing Pre-Organization in Bivalent Aptamers
Xiaoli Hu1, Linlin Tang1, Mengxi Zheng2
1Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
Journal of the American Chemical Society
|March 4, 2022
Summary
Researchers developed a DNA scaffold strategy for designing rigid bivalent aptamers. This method precisely controls ligand positioning, enhancing binding avidity to target molecules.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Multivalent interactions enhance binding avidity in molecular design.
- Rigid scaffolds are crucial for controlling ligand orientation and spatial positioning.
- Existing methods lack general rules for designing simple, rigid DNA scaffolds for multivalent ligands.
Purpose of the Study:
- To develop a crystal structure-guided strategy for rational design of rigid bivalent aptamers.
- To achieve precise control over spatial separation and orientation of aptamer moieties.
- To enable simultaneous binding of aptamer moieties to target proteins in native conformations.
Main Methods:
- Utilized a crystal structure-guided approach for rational design.
- Engineered a rigid DNA scaffold to join two aptamer moieties.
- Characterized the binding of the bivalent aptamer to a target protein.
Main Results:
- Successfully designed a rigid bivalent aptamer with controlled spatial arrangement.
- Demonstrated that the bivalent aptamer binds simultaneously to the target protein.
- Observed significantly enhanced binding avidity compared to monovalent designs.
- Confirmed aptamer moieties maintain native conformations upon binding.
Conclusions:
- The crystal structure-guided strategy enables rational design of rigid multivalent aptamers.
- Precise spatial control over aptamer moieties enhances binding avidity.
- This approach offers a potentially generalizable method for designing multivalent aptamers.
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