Biologics such as proteins and siRNA are important classes of therapeutics.  These biomolecules are highly evolved for specific functions, and as a result, have been approved for clinical use.  However, proteins and siRNA do have significant formulation and pharmacological difficulties associated with their use.  The addition of excipients or attachment of polymer chains enhances stabilization or pharmacokinetics, respectively.  We are preparing polymers to address both issues.  Our strategy is to prepare polymers that enhance stabilization and can also attach covalently to the biomolecules.  We have achieved this by synthesizing polymers with reactive chain ends that mimic natural disaccharides and polysaccharides.  For example, glycopolymers that contain trehalose units are made.  In addition, polymers that are charged and mimic heparin are synthesized.  The polymers are prepared using reversible addition-fragmentation chain transfer polymerization with protein-reactive chain transfer reagents.  The cytotoxicities of the polymers are ascertained in cell culture.  The polymers are then conjugated to proteins and siRNA via reversible and irreversible bonds.  The activities of the resulting conjugates are determined after subjection to environmentally- and therapeutically-relevant stresses.   Synthesis of the polymers and conjugates, and applicability in medicine will be discussed.

Polymers that mimic natural saccharides for stabilization of biomolecules

246th National Meeting (2013)

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