Structural effects on ss- and dsDNA recognition by a beta-hairpin peptide

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• The specific interactions governing peptide-nucleic acid binding are critical for understanding biological processes and designing novel biomaterials.
• Previous studies established that a designed beta-hairpin dimer binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) via distinct mechanisms, primarily involving aromatic/electrostatic and electrostatic interactions, respectively.

Purpose of the Study:

• To investigate the influence of beta-hairpin folding and chirality on binding affinity and selectivity towards ssDNA versus dsDNA.
• To elucidate the structural factors contributing to the selective recognition of different DNA forms.
• To inform the design of advanced biomimetic receptors for nucleic acid applications.

Main Methods:

• Utilized binding studies to quantify the interactions between a designed beta-hairpin dimer and both ssDNA and dsDNA.
• Systematically altered peptide folding and chirality to assess their impact on binding parameters.
• Analyzed dissociation constants and binding modes to determine the roles of structure and stereochemistry.

Main Results:

• Peptide folding was found to be indispensable for binding to both ssDNA and dsDNA.
• Chirality of the beta-hairpin significantly affected binding to dsDNA but showed no discernible impact on ssDNA binding.
• These findings highlight distinct binding mechanisms and driving forces for ssDNA and dsDNA interactions.

Conclusions:

• Beta-hairpin structure, encompassing both folding and chirality, plays a crucial role in the affinity and selectivity of DNA binding.
• The differential effects of folding and chirality on ssDNA versus dsDNA binding underscore the complexity of peptide-nucleic acid recognition.
• These insights pave the way for the rational design of peptide-based receptors with tailored DNA-binding specificities.