Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58
Ameya Gokhale1, Thomas K Weldeghiorghis, Veena Taneja
1Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71201, United States.
Journal of Medicinal Chemistry
|July 16, 2011
Summary
Researchers designed peptides to block cell adhesion interactions between CD2 and CD58 proteins, crucial for immune responses. Peptides 6 and 7 effectively inhibited this interaction, showing potential for therapeutic applications.
Area of Science:
- Immunology
- Structural Biology
- Biochemistry
Background:
- Cell adhesion molecules like CD2 and CD58 are vital for immune responses.
- Protein-protein interactions mediate cell adhesion, making them targets for therapeutic modulation.
Purpose of the Study:
- To design and synthesize peptides that inhibit the CD2-CD58 cell adhesion interaction.
- To investigate the structural basis of peptide-mediated inhibition.
Main Methods:
- Peptide design based on discontinuous epitopes of the CD2 protein's β-strand region.
- Solution structure determination using Nuclear Magnetic Resonance (NMR) and molecular dynamics simulations.
- Inhibition assays including E-rosetting and lymphocyte epithelial adhesion assays.
Main Results:
- Peptides incorporating β-sheet-inducing sequences or turn mimetics were synthesized.
- Peptides 6 and 7 demonstrated significant inhibition of cell adhesion, with IC50 values of 7 nM and 11 nM, respectively.
- NMR and molecular modeling confirmed that peptides 6 and 7 adopt a β-hairpin structure in solution.
Conclusions:
- Designed peptides can effectively modulate CD2-CD58 mediated cell adhesion.
- The β-hairpin structure of peptides 6 and 7 is crucial for their inhibitory activity.
- These peptides represent promising candidates for therapeutic intervention in immune-related disorders.
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