Aβ17-20 Peptide-Guided Structuring of Polymeric Conjugates and Their pH-Triggered Dynamic Response

• Published in: Macromolecular bioscience 2015-10, Vol.15 (10), p.1447-1456
• Main Authors: Kumar, Sonu, Bheemireddy, Varun, De, Priyadarsi
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - chemistry; Chromatography, Gel; Circular Dichroism; conformational analysis; drug delivery systems; graft copolymers; Hydrogen-Ion Concentration; Microscopy, Electron, Scanning; Molecular Dynamics Simulation; nanoparticles; Particle Size; peptides; Polymers - chemistry; Proton Magnetic Resonance Spectroscopy; Solutions; Spectroscopy, Fourier Transform Infrared
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201500134

The tetrapeptide segment LVFF from the central hydrophobic core of amyloid β‐peptide, Aβ17–20, based methacrylate monomer was polymerized via reversible addition‐fragmentation chain transfer (RAFT) polymerization to afford well‐defined side‐chain peptide polymers. The polymer was transformed to carry primary amino groups in the peptide terminals, depicting pH‐responsiveness and was further modified to provide amphiphilic graft copolymer‐based nanocarriers with pH‐triggered dynamic dye release capability. The polymers acquired α‐helical conformation guided by Aβ17–20 peptide. Computational studies were performed to investigate the secondary interactions of the peptide‐based materials. A “Smart” biohybrid polymer based on amyloidogenic short peptide segment is Aβ17‐20. They are synthesized via reversible addition‐fragmentation chain transfer (RAFT) method. The formation of unique nanostructures and α‐helix‐based secondary structures are obtained governed by peptide moieties. Post‐polymerization modification approach is used to prepare poly(ethylene glycol) (PEG)ylated amphiphilic graft copolymer having imine linkage, which self‐assemble into nanoparticles offering pH‐triggered drug‐release behavior.