Eric V. Anslyn received his BS in chemistry from the California State University Northridge in 1982. He performed his thesis studies under the direction of Robert Grubbs at the California Institute of Technology, receiving a PhD in 1987. Afterwards, he was an NSF post-doctoral fellow at Columbia University, working with the late Ronald Breslow. From there he started as an assistant professor of chemistry at the University of Texas at Austin in 1989. At UT Austin he rose through the ranks to currently hold the Welch Regents Chair of Chemistry, and is a University Distinguished Teaching Professor, as well as a Howard Hughes Medical Institute Professor. He has received numerous awards, including the Izatt Christiansen Award for Macrocyclic and Supramolecular Chemistry, the Czarnik Award for Molecular Sensing, the Edward Lette Award, the Cope Scholar Award, and the James Flack Norris Award in Physical Organic Chemistry, the later three being from the American Chemical Society. His research is broadly in the areas of physical organic chemistry and supramolecular chemistry with a specialization on molecular sensing, mechanistic organic chemistry studies, and most recently soft-materials and sequence defined polymers. He is a co-author of the graduate level textbook entitled “Modern Physical Organic Chemistry”.
There is little argument that many of the grand achievements of biotechnology, biochemistry, and chemical biology stem from advances in synthetic organic chemistry embodied in the development of solid-phase synthetic approaches for proteins and nucleic acids. Of equal importance to the synthesis of the biopolymers, however, are methods for their sequencing. Revolutions in nucleic acid sequencing have led to single molecule and Next-Gen parallel methods. Similar advances in protein sequencing have lagged behind. In collaboration with the Marcotte group at UT Austin, we have created a single-molecule peptide sequencing routine referred to as fluorosequencing. Therein, peptides are N-terminal captured, the amino acids selectively labelled with fluorophores, C-terminal differentiated, and then placed on TIRF microscope for rounds of Edman degradation. The development and implementation of the organic chemistry necessary in the method will be discussed. On other topic, the ribosome is Nature’s synthesis machine for creating sequence-defined polyamides, i.e., peptides/proteins. This machinery has previously only been shown to generate analogous linkages, such as esters. Given this limitation, we have extended Nature’s machinery to make repetitions of complex hetercyclic rings, such as pyridazinones. Further, the sequencing of sequence-defined polymers, other than nucleic acids and proteins, shows promise as a new paradigm for data storage. We have devised the first use of oligourethanes for storing and reading encoded information. As a proof of principle, the approach will be described by using a text passage from Jane Austen’s Mansfield Park. It was encoded in oligourethanes and reconstructed via chain-end degradation sequencing. We developed Mol.E-coder, a software tool that utilizes a Huffman encoding scheme to convert the character table to hexadecimal. The passage was capable of being reproduced wholly intact by a third-party, without any purifications or the use of MS/MS, despite multiple rounds of compression, encoding, and synthesis. Overall, this presentation will highlight the interplay and utility of synthesis and sequencing in sequence-defined polymers.