Multivalent macrocyclic hosts: histone surface recognition, guest binding, and delivery by cyclophane-based...

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Biochemistry

Background:

• Resorcinarene oligomers are explored as hosts for proteins and hydrophobic molecules.
• Designing multivalent host systems can enhance molecular recognition.
• Histone proteins are key components of eukaryotic chromatin.

Purpose of the Study:

• To design and synthesize novel cyclophane-based resorcinarene oligomers.
• To investigate the binding capabilities of these oligomers towards histone proteins.
• To evaluate the affinity for hydrophobic guests and their carrier functions.

Main Methods:

• Synthesis of cyclophane-based resorcinarene tetramer (4) and dodecamer (12).
• Surface plasmon resonance (SPR) measurements for protein binding constants.
• Fluorescence spectroscopy for hydrophobic guest binding and carrier studies.

Main Results:

• Oligomers 4 and 12 exhibited potent recognition of histone proteins with high binding constants (1.3x10^7 M^-1 and 8.4x10^7 M^-1, respectively).
• Binding affinities for histone were significantly higher (31- to 200-fold) compared to untethered resorcinarene, demonstrating multivalency effects.
• The oligomers effectively captured hydrophobic guests (e.g., 6-p-toluidinonaphthalene-2-sulfonate) with binding constants up to 2.5x10^4 M^-1.
• Resorcinarene oligomers functioned as effective carriers for guests to histone surfaces.

Conclusions:

• Cyclophane-based resorcinarene oligomers represent a new class of host molecules with strong protein and hydrophobic guest recognition.
• The multivalent architecture significantly enhances binding affinities due to synergistic effects.
• These oligomers show promise as molecular recognition agents and drug/cargo delivery systems.