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The Krishnamurthy Lab

Research

FIgure 4

Origins of Life Studies: We utilize the tools of synthetic organic chemistry and methodology to try and understand the chemical process of life: its origins, its evolution and its current state.

  • Working within the constraints of primordial chemistry we delineate the types of precursor building blocks and organo-chemical reactions that have the potential to give rise to bio- and proto-biomolecules of interest. Then, we investigate how these molecules could evolve (e.g. transform or self-assemble) to confer certain benefits (e.g. stability and function). These investigations are expected to contribute to an understanding as to how the currently functioning biomolecules can come into existence starting from simpler precursors.
  • We are interested in mapping the landscape of potentially primordial informational oligomers that contain backbones, recognition elements and linker groups that are quite different from the canonical structures. Expanding on the approach “Chemical Etiology of Nucleic Acid Structure” codified by Professor A. Eschenmoser, we continue - to conceive (by chemical reasoning) potentially natural alternatives to the nucleic acid structure, to synthesize such alternatives by chemical methods, and to systematically compare them with the natural nucleic acids with respect to those chemical properties that are fundamental to the biological function of RNA and DNA.

Such an endeavor can result not only in creating a perspective for understanding nature's choice of its molecular functionaries, but also in the development of new synthetic strategies and discovery of novel chemistries.

RNApentuloNA

Molecular Bio-mimicry and Chemical Biology: We are interested in expanding the repertoire of artificial informational polymers with a goal to relate the structural variation with the expression of emergent properties.

  • Inspired by, and building on, the concepts uncovered in the studies of potentially natural alternatives to RNA, we have begun to identify novel non-natural alternative structures of RNA and DNA that are thought to possess interesting properties both from the structural and functional point of view. Our objective is to synthesize these unorthodox oligomers and investigate their properties and structure.
  • The study of how these non-natural alternative informational polymers interact with enzymes, and behave in a cellular environment, is of interest in the context of chemical biology. To understand how they affect and interfere with cellular processes and function, and how they are expressed in a cellular environment is expected to contribute to our understanding of manipulating biological processes – ultimately leading to modulation or creation of new biological functions.

The overall thrust of these investigations is to uncover the requirements that should be met in the quest towards the development of alternative biology.

Scheme 7

Chemical Therapeutics: The alternative targets and intermediates produced in the above endeavors provide a new, and rich, source of structurally and functionally wide-ranging molecules that would be useful from a medicinal chemistry viewpoint. We are working closely with groups at TSRI to screen and evaluate the biological activity of these novel compounds and intermediates synthesized in our laboratories.