Poly(propargyl-L-glutamate) (PPLG), and similar functionalizable polypeptides subsequently introduced, have enabled a broad range of new approaches to design of artificial polypeptide systems with properties that engage or mimic biology.  The resulting polymers can serve as interesting scaffolds for the generation of amphiphilic macromolecules capable of pH responsive drug delivery or oligomeric systems that encapsulate siRNA.   Furthermore, these systems can be modified to optimize their interactions with protein-RNA complexes. The pre-encapsulation of the translational proteins complexed with mRNA can enhance mRNA translation within cells by multifold in comparison to release of mRNA alone.  For example, we found that a unique series of polypeptides with variable charged side chain structures can enhance encapsulation of mRNA with EIF4E, with optimal systems yielding 70 to 80 times that of the mRNA alone. A key to these polymers is their ability to cooperatively bind RNA with the associated protein machinery needed for translation together to enhance translation. More recently, we have found similar kinds of enhancements for the delivery of siRNA via co-complexation with the Ago-2 protein to create a pre-assembled version of RISC complex, and with Poly-A binding protein with mRNA.     These systems, and the potential role of such complexes in medical applications, will be discussed.<br/>

Polypeptide, RNA, and protein co-assemblies as delivery systems

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.