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Chemistry

Faculty

Luke J. Leman, Ph.D.

Assistant Professor of Chemistry
Department of Chemistry
California Campus
Laboratory Website
lleman@scripps.edu
(858) 784-2711

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

B.A., Biochemistry/Molecular, Cellular, and Developmental Biology, University of Colorado; Boulder, CO, 2001
Ph.D., Chemistry, The Scripps Research Institute; La Jolla, CA, 2006

Selected References

Maolanon, A. R., Kristensen, H. M. E., Leman, L. J., Ghadiri, M. R., and Olsen, C. A. Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes. ChemBioChem. 2017, 18, 5-49.

Leman, L. J. and Ghadiri, M. R. "Potentially Prebiotic Synthesis of α-Amino Thioacids in Water." Synlett 2017, 28, 68-72.

Leman, L. J., Huang, Z.-Z., and Ghadiri, M. R. "Peptide bond formation in water mediated by carbon disulfide." Astrobiology 2015, 15, 709-716.

Leman, L. J. "The potential of apolipoprotein mimitic peptides in the treatment of atherosclerosis." Clin. Lipidol. 2015, 10, 215-217.

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.

Leman, L. J., Maryanoff, B. E., and Ghadiri, M. R. "Molecules That Mimic Apolipoprotein A-I: Potential Agents for Treating Atherosclerosis." J. Med. Chem. 201457, 2169-2196. 

Zhao, Y., Imura, T., Leman, L. J., Curtiss, L. K., Maryanoff, B. E., and Ghadiri, M. R. "Mimicry of High-Density Lipoprotein: Functional Peptide-Lipid Nanoparticles Based on Multivalent Peptide Constructs." J. Am. Chem. Soc. 2013135, 13414-13424.

Vickers, C. J., Olsen, C. A., Leman, L. J., and Ghadiri, M. R. "Discovery of HDAC inhibitors that lack an active site Zn2+-binding functional group." ACS Med. Chem. Lett. 20123, 505-508.

Olsen, C. A., Montero, A., Leman, L. J., and Ghadiri, M. R. "Macrocyclic peptoid-peptide hybrids as inhibitors of class I histone deacetylases." ACS Med. Chem. Lett. 20123, 749-753.

Hutt, D. M., Olsen, C. A., Vickers, C. J., Herman, D., Chalfant, M. A., Montero, A., Leman, L. J., Burkle, R., Maryanoff, B. E., Balch, W. E., et al. "Potential agents for treating cystic fibrosis: Cyclic tetrapeptides that restore trafficking and activity of ΔF508-CFTR." ACS Med. Chem. Lett. 20112, 703-707.

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.

Ura, Y., Al-Sayah, M., Montenegro, J., Beierle, J. M., Leman, L. J., and Ghadiri, M. R. "Dynamic polythioesters via ring-opening polymerization of 1,4-thiazine-2,5-diones." Org. Biomol. Chem. 2009, 7, 2878-2884.

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.

Yadav, M. K., Leman, L. J., Price, D. J., Brooks, C. L., III, Stout, C. D., and Ghadiri, M. R. "Coiled coils at the edge of configurational heterogeneity. Structural analyses of parallel and antiparallel homotetrameric coiled coils reveal configurational sensitivity to a single solvent-exposed amino acid substitution." Biochemistry 2006, 45, 4463-4473.

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.

Yadav, M. K., Redman, J. E., Leman, L. J., Alvarez-Gutierrez, J. M., Zhang, Y., Stout, C. D., and Ghadiri, M. R. "Structure-based engineering of internal cavities in coiled-coil peptides." Biochemistry 2005, 44, 9723-9732.

Leman, L., Orgel, L., and Ghadiri, M. R. "Carbonyl sulfide-mediated prebiotic formation of peptides." Science 2004, 306, 283-286.

Links

Study Suggests Component of Volcanic Gas May Have Played a Significant Role in the Origins of Life on Earth

Team Creates Simple Chemical System that Mimics DNA

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