Supramolecular ligands: monomer structure and protein ligation capability

Area of Science:

• Supramolecular Chemistry
• Biochemistry
• Dye Chemistry

Background:

• Proteins interact with ligands, but the supramolecular nature of ligands is often lost.
• Bis azo dyes are known to self-assemble in aqueous solutions.
• Understanding self-assembly is key to designing ligands that retain their supramolecular characteristics upon protein interaction.

Purpose of the Study:

• To define the chemical structures of self-assembling compounds in water.
• To investigate how these compounds interact with proteins as single ligands while preserving supramolecular nature.
• To correlate self-assembly properties with protein ligation capabilities.

Main Methods:

• Studied ligation of Congo red and its derivatives to proteins.
• Determined three parameters: assembly product stability, binding to heat-denatured human IgG, and binding to native rabbit antibodies.
• Investigated other dyes like Evans blue, Trypan blue, bis-ANS, and ANS for comparison.

Main Results:

• Rigid, elongated, symmetric molecules with large non-polar fragments formed ribbon-like supramolecular structures.
• These structures exhibited ligation properties linked to their self-assembling tendency.
• Compounds with non-bis azo dye structures showed no ligation capability, especially with native proteins.
• Binding to denatured proteins was less restrictive, allowing complexation of non-assembled molecules.

Conclusions:

• Self-assembly in bis azo dyes is crucial for their protein ligation properties.
• Molecular structure, particularly symmetry and the non-polar component, dictates self-assembly and ligation.
• Denatured proteins offer more accessible binding sites for both assembled and non-assembled ligands compared to native proteins.