Exploiting Oligo(amido amine) Backbones for the Multivalent Presentation of Coiled-Coil Peptides

Area of Science:

• Supramolecular Chemistry
• Polymer Science
• Bioconjugation

Background:

• Coiled-coil formation is crucial in biological systems.
• Designing synthetic systems to mimic or control coiled-coil assembly is challenging.
• Peptide-polymer conjugates offer a platform for precise molecular architecture.

Purpose of the Study:

• To investigate coiled-coil formation in mono- and divalent peptide-polymer conjugates.
• To explore the role of a polymer backbone as a template for peptide assembly.
• To understand how intramolecular and heteromeric coiled-coil structures form.

Main Methods:

• Solid-phase synthesis of sequence-defined peptide-polymer conjugates.
• Design of heteromeric peptides (K and E sequences) attached to a polymer backbone.
• Characterization of coiled-coil formation using spectroscopic and structural methods (implied).

Main Results:

• Monodisperse peptide-polymer conjugates with defined peptide spacing were synthesized.
• Monovalent K-peptide conjugates formed heteromeric coiled-coils with complementary E peptides.
• Divalent systems unexpectedly formed intramolecular homomeric coiled-coils, templated by the polymer.
• Addition of E peptide induced rearrangement of intramolecular assemblies into heteromeric coiled-coil-polymer aggregates.

Conclusions:

• Polymer backbones can act as templates to induce intramolecular peptide assembly by increasing local concentration.
• This templating effect can overcome unfavorable thermodynamics for homomeric coiled-coil formation.
• The system demonstrates a switchable assembly mechanism, transitioning from intramolecular to heteromeric structures.