Molecular self-assembly of amino acid pairing peptides and their derivatives

点击翻译按钮获取中文摘要

Molecular self-assembly has been the hallmark of nanotechnology research, with applications in various engineering and biomedical processes. We have developed a new class of self-assembling biomolecules: amino acid pairing (AAP) peptides. Just like the base pairing in a DNA double helix, amino acid pairing allows self-assembly of peptide molecules, leading to desired functional nanostructures. The AAP peptides not only possess specific molecular functions (e.g., stimuli-responsiveness, micro-environment recognition, and cell membrane targeting) but also derive surfactant-like or amphiphilic characteristics from their unique amino acid sequences for molecular self/co-assembly. These peptides and their assembled nanostructures, or nano-vehicles, are able to interact with other molecules, e.g., hydrophobic compounds as in anticancer drugs, hydrophilic molecules as in DNAs and siRNAs (short interfering RNAs), and different engineering surfaces. They have been found to be useful in drug and gene delivery. In this proposal, we propose to expand our research on peptide self/co-assembly and nano-vehicle design. Our short term objectives are to: (1) explore molecular design and nano-structure formation of amino acid pairing peptides and their derivatives; (2) evaluate stimuli-responsiveness or micro-environment recognition of designed amino acid pairing peptides and their self-assembled nano-vehicles; (3) elucidate peptide and cell membrane interaction, where self-assembled nanostructures and their responses to the unique surface properties of cell membranes will be uncovered; (4) investigate interaction/hybridization of peptide and graphene or their derivatives, where molecular details will be revealed on the peptide-graphene complexation, to achieve graphite exfoliation and functionalization of graphene oxide derivatives. Our long term objectives are to: (1) establish a cluster of molecular engineering tools, the first time in the field, to design peptide primary, secondary, tertiary and nano-structures via the amino acid pairing principle; (2) construct novel nano-vehicles via peptide amino acid pairing or pairing between peptide residues and functional groups/moieties of co-assembled molecules, where maximum molecular cargo loading, stimuli-responsiveness, targeted and controlled release can all be achieved. These multi-functional molecular machines or nano-vehicles will find a wide range of biomedical engineering applications, including biosensors, surface modification, and targeted drug and gene delivery. We plan to start a spin-off company at the end of the project to commercialize developed technologies. The student trainees may be involved in this endeavor, but they will be skilled for many other high tech jobs, especially in nanotechnology, chemical molecular design and nanomedicine, all critical to the future Canadian economy.