An Exponential Amplification Strategy for Precision Polymeric Materials
Abstract
Nature is able to exponentially replicate, translate, and evolve precision polymers (e.g. DNA) to create materials capable of advanced molecular recognition, sensing, and self-assembly. Sophisticated protein machinery, which includes translation, replication, and error correction enzymes, is crucial in enabling these processes. Nevertheless, such replication machinery is non-existent for most synthetic polymers. Thus, current translation and replication approaches for man-made, sequence-defined macromolecules are often error prone and inefficient. This research therefore aims to overcome some of the current fundamental limitations toward exponential polymer replication. It focuses, in particular on reducing replication errors and enhancing replication efficiency. It would likely enable new avenues to exponentially amplify synthetic polymers with different backbones and recognition alphabets. This advance would bring with it the possibility to synthesize precision macromolecules in a more sustainable fashion from preexisting templates, rather than from scratch. Furthermore, with the vision to amplify these structures exponentially, diverse sets of polymers (chemical libraries) capable of direct, relatively fast in vitro evolution could likely be created. Note that being able to build such directly evolvable chemical libraries is relevant for homeland security and soldier protection, e.g. to detect biochemical threats. To meet the fundamental challenge of evolving synthetic precision polymers, this research aims to discover how the accuracy of polymer translation/replication can be enhanced. The central goal is to find general design rules describing how reversible bond formation between different building blocks affects the error-rates of translations/replications. In principle, the presence of such reversible bonds allows replication errors to be corrected, which likely leads to lower error rates. Nevertheless, before serving as new templates in following replication rounds, reversible daughter polymers need to be converted to their corresponding, irreversibly connected counterparts. Different types of reversible bonding will thus be explored and coupled with unique schemes to selectively arrest the reversibility of these bonds during exponential amplification cycles. In addition, this proposal also presents a general strategy to overcome product inhibition between daughter and template strands (which has, thus far, reduced the efficiencies of most synthetic approaches toward exponential polymer replication). The proposed approach focuses on key physical interactions determining the accuracy of replication for different recognition groups and polymer backbones. It is designed to be general to allow polymers with different functional group sequences Ñ arranged in linear, cyclic, and possibly even branched architectures Ñ to be replicated. Ultimately, the proposed research is devised to discover general design rules for the creation of sequence-defined, functional, synthetic materials, which can be amplified in an exponential fashion. It could, ultimately, lead to a new approach to synthesize precision macromolecules from preexisting templates and enable the direct evolution of synthetic macromolecules in the test tube.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 14, 2019
- Source ID
- W911NF1810080
Entities
People
- Severin T Schneebeli
Organizations
- Army Contracting Command
- United States Army
- University of Vermont