Lucas Leman, PhD
Research Focus
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.
Education
Ph.D. (Chemistry), Scripps Research, 2006B.A. (Biochemistry / Molecular, Cellular, and Developmental Biology), University of Colorado Boulder, 2001
Selected References
Frenkel-Pinter, M.; Haynes, J. W.; Mohyeldin, A. M.; C, M.; Sargon, A. B.; Petrov, A. S.; Krishnamurthy, R.; Hud, N. V.; Williams, L. D.; Leman, L. J. "Mutually stabilizing interactions between proto-peptides and RNA." Nat. Commun. 2020, 11, 3137.
Chen, P. B.; Black, A. S.; Sobel, A. L.; Zhao, Y.; Mukherjee, P.; Molparia, B.; Moore, N. E.; Aleman Muench, G. R.; Wu, J.; Chen, W.; et al. "Directed remodeling of the mouse gut microbiome inhibits the development of atherosclerosis." Nat. Biotechnol. 2020.
Frenkel-Pinter, M.; Samanta, M.; Ashkenasy, G.; Leman, L. J. "Prebiotic peptides: Molecular hubs in the origin of life." Chem. Rev. 2020, 120, 4707-4765.
Frenkel-Pinter, M.; Haynes, J. W.; Martin, C.; Petrov, A. S.; Burcar, B. T.; Krishnamurthy, R.; Hud, N. V.; Leman, L. J.; Williams, L. D. "Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions." Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 16338-16346.
Mukherjee, P.; Leman, L. J.; Griffin, J. H.; Ghadiri, M. R. "Design of a DNA-programmed plasminogen activator." J. Am. Chem. Soc. 2018, 140, 15516-15524.
Beierle, J. M.; Ura, Y.; Ghadiri, M. R.; Leman, L. J. "Templated self-assembly of dynamic peptide nucleic acids." Biochemistry 2018, 57, 160-172.
Zhao, Y.; Leman, L. J.; Search, D. J.; Garcia, R. A.; Gordon, D. A.; Maryanoff, B. E.; Ghadiri, M. R. "Self-assembling cyclic D,L-alpha-peptides as modulators of plasma HDL function. A supramolecular approach toward antiatherosclerotic agents." ACS Cent. Sci. 2017, 3, 639-646.
Zhao, Y., Black, A. S., Bonnet, D. J., Maryanoff, B. E., Curtiss, L. K., Leman, L. J., and Ghadiri, M. R. "In vivo efficacy of HDL-like nanolipid particles containing multivalent peptide mimetics of apolipoprotein A-I." J. Lipid Res. 2014, 55, 2053-2063.
Ura, Y., Beierle, J. M., Leman, L. J., Orgel, L. E., and Ghadiri, M. R. "Self-assembling sequence-adaptive peptide nucleic acids." Science 2009, 325, 73-77.
Huang, Z.-Z., Leman, L. J., and Ghadiri, M. R. "Biomimetic catalysis of diketopiperazine and dipeptide syntheses." Angew. Chem., Int. Ed. 2008, 47, 1758-1761.
Leman, L. J., Weinberger, D. A., Huang, Z.-Z., Wilcoxen, K. M., and Ghadiri, M. R. "Functional and mechanistic analyses of biomimetic aminoacyl transfer reactions in de novo designed coiled coil peptides via rational active site engineering." J. Am. Chem. Soc. 2007, 129, 2959-2966.
Wilcoxen, K. M., Leman, L. J., Weinberger, D. A., Huang, Z.-Z., and Ghadiri, M. R. "Biomimetic catalysis of intermodular aminoacyl transfer." J. Am. Chem. Soc. 2007, 129, 748-749.
Leman, L. J., Orgel, L. E., and Ghadiri, M. R. "Amino acid dependent formation of phosphate anhydrides in water mediated by carbonyl sulfide." J. Am. Chem. Soc. 2006, 128, 20-21.
Leman, L., Orgel, L., and Ghadiri, M. R. "Carbonyl sulfide-mediated prebiotic formation of peptides." Science 2004, 306, 283-286.
Links
Team Creates Simple Chemical System that Mimics DNA
A chemical clue to how life started on Earth
Scientists Create Mimic of 'Good' Cholesterol to Fight Heart Disease and Stroke