Biomolecular Constructs as Building Blocks of Soft Nanoscale Materials

Case ID: 110

Web Published: 2/6/2021

NU 2017-032

INVENTORS
SonBinh Nguyen*
Nathaniel Rosi* (Univ of Pittsburgh)

SHORT DESCRIPTION
A highly tunable assembly platform that enables the modular synthesis of programmable peptide-oligonucleotide chimeras to assemble into vesicles or 1D fibres.

BACKGROUND
Few classes of material building blocks exhibit the programmability offered by nucleic acids and peptides. These macromolecules offer a distinct set of material-assembly properties. Nucleic acids exhibit unrivalled site-specificity that is based on their sequence-specific base-pairing interactions between complementary oligonucleotides, allowing for the construction of highly intricate nanoscale architectures and spherical nucleic acid-based assemblies. Based on their rich diversity of amino acid sequences, peptides have also been extensively exploited as assembly components, exhibiting highly modular assembly and substrate-recognition capabilities. For example, a 10-mer peptide built from natural amino acids can have 2010 possible sequences. It stands to reason then that molecular building blocks composed of both nucleic acids and peptides would have the potential to assemble into materials that bear heretofore unobserved features and properties that may lead to new breakthrough applications in various fields.

ABSTRACT
While DNA-peptides conjugates have previously been made, most often the property of either component dominates. A collaborative team of researchers from Northwestern and the University of Pittsburgh have developed a new class of DNA-peptide hybrids that link together by an organic core, called triblock peptide-oligonucleotide chimeras (POCs), with well-defined valency and geometry. They have also developed design rules that can predict and logically alter POC assembly morphology, enabling a new class of modular and programmable biomolecular building blocks for design and construction of highly tunable soft nanoscale materials that can undergo morphological transformations in response to external stimuli. They show that a plurality of factors, including oligonucleotide length, peptide secondary structure, and ionic strength of the assembly medium, significantly influence POC assembly and direct the formation of either spherical vesicles or 1D fibers. As a result, they have a composite property that takes advantage of the properties of both of the peptide and DNA components as well as the directionality/multiplicity of the core. Therefore, these can behave as new biopolymers with functions that derived from the synergistic coupling of the properties of the each component. Depending on the environment (or in the presence of a stimuli), these materials can assemble into different morphology or change shapes, thus allowing for their use in a broad range of applications.

APPLICATIONS

Diagnostic and sensing
Drug Delivery
Nucleic acid therapeutic
Stimuli-responsive materials for sensing, camouflaging, payload-release

ADVANTAGES

Tunable (sequential or orthogonal) coupling of peptide and DNA onto an organic core using simple chemistry
High-yield synthesis
Responsive to environment (pH, salt concentration, temperature, etc.) and stimuli (DNA aptamers, small molecules, any peptide-recognizable epitopes)

PUBLICATION
Merg A, Thaner R, Mokashi-Punekar S, Nguyen SB and Rosi N (2017) Triblock Peptide-Oligonucleotide Chimeras (POCs): Programmable Biomolecules for the Assembly of Morphologically Tunable and Responsive Hybrid Materials. Chemical Communications. 53: 12221.

IP STATUS
A US patent application has been filed.