OLIGONUCLEOTIDE-BASED TUNING OF PORE-FORMING PEPTIDES FOR INCREASING PORE SIZE, MEMBRANE AFFINITY, STABILITY, AND ANTIMICROBIAL ACTIVITY

摘要

Pore-forming peptides or proteins modified utilizing DNA nanotechnology, which provides definition and control of pore size, an increase in stability when inserted in a lipid membrane, and membrane affinity. Chemical modifications are easily made on the compound through hybridization to the oligonucleotide attached to the peptide or protein. The compound can hybridize to a DNA template thereby defining the number of monomers assembled to a pore and thus the size of the formed pore. The DNA template can range from a unique single strand composed of multiple hybridization sites separated by flexible linkers to a complex rigid DNA nanoconstruct, such as a DNA origami-based ring, serving as a scaffold for pore formation. Hydrophilic modification at the transmembrane segment or terminus of the peptide provides long-lived pores and keeps the compound in a membrane-spanning conformation.