Self-Replicating Nucleic Acids

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This project will continue work on the chemical synthesis of polymers that can both carry information in their sequence and replicate that information chemically without using enzymes. These experiments are inspired by the desire to understand the emergence of information carrying molecules such as RNA during the origin of life on earth. Basic chemical principles are used to design simple variants of RNA and DNA that may be capable of chemical replication, such as a family of nucleic acids in which the hydroxyl nucleophile is replaced with an amino group, which is a stronger nucleophile. This change, coupled with the use of more active leaving groups as well as nucleobases that enhance duplex stability, should lead to faster chemical copying of template sequences. The project will also explore ways in which replication may be accelerated through the use of simple catalysts, or through localization to mineral surfaces or membrane vesicles. With this award, the Organic and Macromolecular Chemistry Program and the Genes and Genome Systems Cluster program are supporting the research of Professor Jack W. Szostak of the Department of Molecular Biology at Massachusetts General Hospital. Professor Szostak's research is aimed at understanding the origin of life on the early earth, a topic that has always attracted great public interest. Because this work explores the connection between chemistry and biology at a very fundamental level, it is also of great interest to students, and will help to attract young people to the chemical sciences.