Sequence-controlled polymers (SCPs) are linear macromolecules whose chemical and physical properties can be programmed with atomic-scale resolution. The development of synthetic routes toward these molecules promises technological breakthroughs in novel materials, nanotechnology, and medicine. However, at this time, synthetic polymerization methods lack efficiency and sequence control. Moreover, they do not approach the accuracy, reproducibility, and control found in nature. To address this grand challenge, this joint effort between Northwestern University and the University of Warwick in the United Kingdom develops chemical (e.g., ring opening polymerization) and biological (e.g., evolution of the translation apparatus) methods towards the cost-effective and high-yielding synthesis of sequence-controlled vinyl polypeptides. Vinyl amino acids will be synthesized and incorporated into natural polymers, endowing biopolymers with new chemical functionality and serving as a model for the synthesis of more complex template-directed SCPs. Specific aims include: (1) synthesis of a library of vinyl amino acids; (2) linking vinyl amino acids to transfer-RNA adapter molecules; (3) synthesis of vinyl polypeptides with complementary chemical and biological approaches; and (4) characterization and application of the properties of vinyl hybrid biomolecules. In the short term, progress towards the production of vinyl SCPs using evolved biological catalysts and chemical methods, as well as vinyl SCP characterization, will enable new applications. By using vinyl functionality as a handle, polypeptides will be tailored to display novel assembly, responsiveness, and catalytic activity. Furthermore, the ability to tune and direct the assembly of vinyl SCPs will allow for the development of a new class of functional biohybrid materials. In the long term, new strategies for SCP synthesis will offer the potential of self-organized materials with greater chemical diversity, tunability, and technological possibilities than presently exist.
The possibilities of producing evolvable, structurally broad synthetic polymers that meld the accuracy and reproducibility of biology with the complexity and diversity of chemistry could ultimately enable the synthesis of new molecule classes not readily attainable by current methods, as well as the exploitation of genetically encoded evolution in the search for functional materials. Beyond fundamental discovery and technology development, the US-UK team will establish and maintain a valuable network that provides for competitive, interdisciplinary, and globally engaged research. This network will train the next cadre of "whole-brain" researchers who are comfortable operating between scientific disciplines, laboratories, and continents. Moreover, by exploring differences between outreach education programs and the use of interactive visual experiences to describe science in the US and in the UK, this network will be of great use in engaging public interest. The team places particular emphasis on women in science and plan to use the transatlantic collaboration to inspire and encourage women to pursue their goals at the interface of biology, engineering, and materials science.
