Leman, Luke J. - The Scripps Research Institute

研究领域

The central theme of our research is to engineer new peptide-based molecules and materials that can interact with biomolecules in useful ways. 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.

近期论文

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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, epub ahead of print, DOI: 10.1194/jlr.M049262 Leman, L. J., Maryanoff, B. E., and Ghadiri, M. R. "Molecules That Mimic Apolipoprotein A-I: Potential Agents for Treating Atherosclerosis." J. Med. Chem. 2014, 57, 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. 2013, 135, 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. 2012, ASAP article. Hutt, D. M., Olsen, C. A., Vickers, C. J., Herman, D., Chalfant, M., Montero, A., Leman, L. J., Burkle, R., Maryanoff, B. E., Balch, W. E., and Ghadiri, M. R. "Potential agents for treating cystic fibrosis: Cyclic tetrapeptides that restore trafficking and activity of ΔF508-CFTR." ACS Med. Chem. Lett. 2011, 2, 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. PMCID: PMC2453064 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.