Exploring Routes to Homochirality in the Synthesis of Biological Polymers

The Scripps Research Institute, La Jolla CA

Investigators

Abstract

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professor Donna G. Blackmond from Scripps Research is studying how exclusively homochiral biological polymers emerged from the chiral building blocks of life. Homochiral molecules exist in only one of two possible mirror-image forms, analogous to our right and left hands. Understanding how homochirality emerged will help us understand the origin of life on Earth. Homochirality is also a critical feature of many modern pharmaceuticals, where administering the incorrect “hand” of a drug may result in unintended biological effects. The current research intends to study how molecular building blocks assemble into homochiral chains of proteins and nucleic acids. The results of this work will shed light on chemical processes that occurred billions of years ago, provide insights into the production of modern pharmaceuticals, and underlie key science teaching moments. The concept of mirror image molecules is fascinating to students and laymen alike because the two molecules that are mirror images of each other can exhibit different properties, such as taste and smell. Demonstrations of homochirality – ranging from the shapes of seashells and the smells of spearmint and rye bread to the search for life in interstellar space – represent an exciting means of bringing fundamental and practical chemistry concepts into the lives of young scientists. A key current challenge is to combine the findings from Blackmond's previous studies on monomeric building blocks with investigations focused on prebiotic reaction networks that assemble biological polymers. These studies will combine experimental organic synthesis and kinetic measurements with computational modeling to determine whether there is a specific chain length at which homochiral chains begin to dominate, leaving heterochiral residues behind. This work will also explore whether peptide-forming reactions may be combined with the peptide-catalyzed kinetic resolution of amino acids to create the first known prebiotically relevant autocatalytic feedback network exhibiting chiral amplification. Finally, these investigations will be expanded to the ligation of nucleic acid monomers in prebiotic processes to form RNA oligonucleotides. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.