NU 2018-151
INVENTORS
Chad Mirkin*
Janet McMillan
Oliver Hayes
SHORT DESCRIPTION
A strategy that utilizes DNA for controlling the association pathway of proteins
BACKGROUND
Supramolecular polymeric materials formed via non-covalent associations, play critical roles in biological functions of living systems; their well defined structure and sophisticated chemical functions make them powerful materials in cellular engineering. There exist methods to synthesize protein polymers, however controlling the pathways for this polymerization is difficult due, in part, to the chemical heterogeneity of protein surfaces which require complex binding events, difficult to mimic in vitro. In contrast, DNA interactions are robust and programmable, providing a highly tailorable bonding motif for controlling the assembly of nanoscale building blocks.
ABSTRACT
Northwestern researchers have developed a strategy to deliberately control polymer growth using tailored DNA sequences as binding motifs. Protein monomers are modified by appending a single oligonucleotide strand to form protein-DNA monomers. Dependent on the DNA sequences appended, the oligonucleotide can take the form of stranded or hairpin, determining whether protein-DNA monomer polymerization occurs in a step-growth or chain-growth fashion, respectively. This polymerization strategy is highly selective and and enables the synthesis of protein-DNA polymers with precise composition and complex architectures, broadening the scope and function of synthetic biomaterials.
APPLICATIONS
Multi-step catalysis of oligomers and polymers
Assembly line biosynthesis
Tissue engineering
Soft-materials with unique bulk physical properties dictated by protein composition
ADVANTAGES
Generalizable strategy through which any protein can be incorporated into polymeric structure
Tailorable molecular weight distributions and architecture
Tailorable inter-protein distance via DNA length changes
PUBLICATION
McMillan, J. et. al. (2018) Programming protein polymerization with DNA. Journal of the American Chemical Society. 140.46: 15950-15956.
IP STATUS
US and international patent applications filed.
Complementary, single-stranded DNA appended to protein monomers Sa and Sb polymerize via a step-growth pathway; hairpin DNA strands appended to protein monomers Haand Hb polymerize via a chain-growth pathway, requiring an initiator strand.