Luke Leman, Ph.D.



Leman, Ph.D.

Assistant Professor of Chemistry, Department of Chemistry, California Campus
Scripps Research Institute

What a Wonderful (RNA-peptide) World: Mutually Stabilizing Interactions between Proto-peptides and RNA


  • Ph.D. (Chemistry), Scripps Research, 2006
  • B.A. (Biochemistry / Molecular, Cellular, and Developmental Biology), University of Colorado Boulder, 2001

The central theme of our research is to engineer new peptide-based molecules and materials that can interact with biomolecules in useful ways. We also explore potentially prebiotic reactions that could have been involved in early chemical evolution. By devising and synthesizing peptides, peptide nucleic acids, and peptidomimetics, we seek to use these molecules as tools to understand biology and treat disease. To accomplish this, we use a combination of biophysical techniques, molecular and cell biology, and chemical synthesis. Our goal is to provide novel applications in the field of molecular and system engineering as well as advance the fundamental understanding of living chemical processes and the origins of complex chemical networks. Current areas of research involve sequence-adaptive dynamic nucleic acid analogs and synthetic nanolipid particles as high-density lipoprotein (HDL)-mimetics.

The origin and evolutionary history of biopolymers has long intrigued scientists. To explore the idea that the tightly intertwined biological roles of RNA and peptides originated in early chemical evolution, we have investigated the production of cationic proto-peptides (depsipeptides and polyesters) in model prebiotic reactions and studied their interactions with RNA. The cationic proto-peptides, either as mixtures from the model prebiotic reactions or synthetically prepared in pure form, were found to engage in direct, mutually-stabilizing interactions with RNA. Certain cationic proto-peptides significantly increased the thermal stability of folded RNA structures; in turn, RNA reduced the rate of hydrolysis of depsipeptide ester bonds by >30-fold. Intriguingly, we observed that the proteinaceous cationic amino acids (Arg, His, and Lys) oligomerized more extensively and produced oligomers that better stabilized RNA duplexes than did the analogous non-proteinaceous cationic amino acids that were studied. These results support a model of biopolymer evolution involving a long co-evolutionary history for polypeptide and nucleic acid that began with rudimentary, mutually stabilizing interactions.