The Development of Amplifiable and Evolvable Unnatural Molecules

Abstract

Abstract : We have developed a new approach to (i) controlling chemical reactivity and (ii) discovering functional synthetic molecules that is based on biosynthesis and molecular evolution in nature. Our approach uses DNA-templated organic synthesis as a surprisingly general means of translating an amplifiable information carrier into a synthetic structure. We have integrated insights into DNA-templated synthesis with synthetic organic chemistry and molecular biology to develop (a) new modes of controlling reactivity that are not possible using existing synthetic methods, (b) multistep small molecule syntheses programmed by DNA sequences, (c) a model for stereoselectivity in DNA-templated synthesis, (d) DNA-templated library synthesis of complex small molecules, and (e) selections for DNA-linked synthetic molecules with protein binding affinity and specificity. These studies have enabled synthetic molecules to participate in powerful processes including translation, selection, and amplification previously available only to biological macromolecules. Our studies represent an entirely new approach to synthesis and discovery that may lead to new synthetic small molecules and polymers with desired properties, as well as to the discovery of new chemical reactions.