Lokey Research Group

Click here for a link to Scott Lokey's complete bibliography.

Q. Nhu N. Nguyen, Joshua Schwochert, Dean J. Tantillo, and R. Scott Lokey. Using 1H and 13C NMR chemical shifts to determine cyclic peptide conformations: a combined molecular dynamics and quantum mechanics approach. In Physical Chemistry Chemical Physics. (2018) doi: 110.1039/c8cp01616j Link

Chad Townsend, Akihiro Furukawa, Joshua Schwochert, Cameron R. Pye, Quinn Edmondson, R. Scott Lokey CycLS: Accurate, whole-library sequencing of cyclic peptides using tandem mass spectrometry. In In Biorganic and Medicinal Chemistry. (2018) doi: 10.1016/j.bmc.2018.01.027 Link

Bockus, AT and Lokey, RS. Bioactive and Membrane-Permeable Cyclic Peptide Natural Products. In the book Practical Medicinal Chemistry with Macrocycles: Design, Synthesis, and Case Studies (Wiley) (2017) doi: 10.1002/9781119092599.ch5 Link

Schwochert, J and Lokey RS. Experimental and Computational Approaches to the Study of Macrocycle Conformations in Solution. In the book Experimental and Computational Approaches to the Study of Macrocycle Conformations in Solution (Royal Society of Chemistry) (2017). http://dx.doi.org/10.1039/9781788010153-00280 Link

Markus Boehm, Kevin Beaumont, Rhys M Jones, Amit S. Kalgutkar, Liying Zhang, Karen Atkinson, Guoyun Bai, Janice A. Brown, Heather Eng, Gilles H. Goetz, Brian R Holder, Bhagyashree Khunte, Sarah Lazzaro, Chris Limberakis, Sangwoo Ryu, Michael J Shapiro, Laurie Tylaska, Jiangli Yan, Rushia Turner, Siegfried S. F. Leung, Mahesh Ramaseshan, David A. Price, Spiros Liras, Matthew P Jacobson, David J. Earp, R. Scott Lokey, Alan M Mathiowetz, and Elnaz Menhaji-Klotz. Discovery of potent and orally bioavailable macrocyclic peptide-peptoid hybrid CXCR7 modulators. J. Med Chem.(2017) doi: 10.1021/acs.jmedchem.7b01028 Link

Pye CR, Bertin MJ, Lokey RS, Gerwick WH, Linington RG. Reply to Skinnider and Magarvey: Rates of novel natural product discovery remain high. Proc Natl Acad Sci. (2017) doi: 10.1073/pnas.1711139114 Link

Hanh Lam, Joshua Schwochert, Yongtong Lao, Tannia Lau, Cameron Lloyd, Justin Luu, Olivia Kooner, Jessica Morgan,Scott Lokey, Victoria Auerbuch. Synthetic cyclic peptomers as type III secretion system inhibitors. Antimicrobial Agents and Chemotherapy. (2017) doi:10.1128/AAC.00060-17 Link

Naylor MR, Bockus AT, Blanco MJ, Lokey RS. Cyclic peptide natural products chart the frontier of oral bioavailability in the pursuit of undruggable targets. Curr Opin Chem Biol. (2017) doi: 10.1016/j.cbpa.2017.04.012 Link

Pye CR, Hewitt WM, Schwochert JA, Haddad TD, Townsend CE, Etienne L, Lao Y, Limberakis C, Furukawa A, Mathiowetz AM, Price DA, Liras S, Lokey RS. Non-Classical Size Dependence of Permeation Defines Bounds for Passive Adsorption of Large Drug Molecules J. Med. Chem. (2017) 10.1021/acs.jmedchem.6b01483 Link

Akihiro Furukawa, Chad E. Townsend, Joshua Schwochert, Cameron R. Pye, Maria A. Bednarek, and R. Scott Lokey Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive Variation in Side Chain Functionality and Backbone Geometry J. Med. Chem. (2016) doi: 10.1021/acs.jmedchem.6b01246 Link

Joshua Schwochert, Yongtong Lao, Cameron R. Pye, Matthew R. Naylor, Prashant V. Desai, Isabel C. Gonzalez Valcarcel, Jaclyn A. Barrett, Geri Sawada, Maria-Jesus Blanco, and R. Scott Lokey. Stereochemistry Balances Cell Permeability and Solubility in the Naturally Derived Phepropeptin Cyclic Peptides ACS Medicinal Chemistry Letters. (2016) doi: 10.1021/acsmedchemlett.6b00100 Link

Bockus AT, Schwochert JA, Pye CR, Townsend CE, Sok V, Bednarek MA, and Lokey RS. Going Out on a Limb: Delineating The Effects of beta-Branching, N-Methylation, and Side Chain Size on the Passive Permeability, Solubility, and Flexibility of Sanguinamide A Analogues. J. Med. Chem.(2015) doi: 10.1021/acs.jmedchem.5b00919 Link

Jessica L. Ochoa, Walter M. Bray, R. Scott Lokey, and Roger G. Linington. Phenotype-Guided Natural Products Discovery Using Cytological Profiling. J. Nat. Prod. (2015) doi: 10.1021/acs.jnatprod.5b00455 Link

Ahlbach CL, Lexa KW, Bockus AT, Chen V, Crews P, Jacobson MP, Lokey RS. Beyond cyclosporine A: conformation- dependent passive membrane permeabilities of cyclic peptide natural products. Fut. Med. Chem. (2015) doi: 10.4155/fmc.15.78. Link

Theodore CM, Lorig-Roach N, Still PC, Johnson TA, Drašković M, Schwochert JA, Naphen CN, Crews MS, Barker SA, Valeriote FA, Lokey RS, Crews P. Biosynthetic products from a nearshore-derived gram-negative bacterium enable reassessment of the kailuin depsipeptides. J. Nat. Prod. (2015) doi: 10.1021/np500840n. Link

Schwochert J, Turner R, Thang M, Berkeley RF, Ponkey AR, Rodriguez KM, Leung SS, Khunte B, Goetz G, Limberakis C, Kalgutkar AS, Eng H, Shapiro MJ, Mathiowetz AM, Price DA, Liras S, Jacobson MP, Lokey RS.Peptide to Peptoid Substitutions Increase Cell Permeability in Cyclic Hexapeptides. Org. Lett. (2015) doi: 10.1021/acs.orglett.5b01162. Link

Bockus AT, Lexa KW, Pye CR, Kalgutkar AS, Gardner JW, Hund KC, Hewitt WM, Schwochert JA, Glassey E, Price DA, Mathiowetz AM, Liras S, Jacobson MP, Lokey RS. Probing the Physicochemical Boundaries of Cell Permeability and Oral Bioavailability in Lipophilic Macrocycles Inspired by Natural Products. J. Med. Chem. (2014) 10.1021/acs.jmedchem.5b00128. Link PDF

Hewitt WM, Leung SSF, Pye CR, Ponkey AR, Bednarek M, Jacobson MP, Lokey RS. Cell-Permeable Cyclic Peptides from Synthetic Libraries Inspired by Natural Products. J. Am. Chem. Soc., 137 (2014) pp. 715-721 Link PDF

Wride DA, Pourmand N, Bray WM, Kosarchuk JJ, Nisam SC, Quan TK, Berkeley RF, Katzman S, Hartzog GA, Dobkin CE, Lokey RS. Confirmation of the Cellular Targets of Benomyl and Rapamycin Using Next-Generation Sequencing of Resistant Mutants in S. Cerevisiae. Mol. BioSyst. 10 (2014) 3179-87. Link PDF

Schwochert J, Pye C, Ahlbach C, Abdollahian Y, Farley K, Khunte B, Limberakis C, Kalgutkar AS, Eng H, Shapiro MJ, Mathiowetz AM, Price DA, Liras S, Lokey RS. Revisiting N-to-O Acyl Shift for Synthesis of Natural Product-like Cyclic Depsipeptides Organic letters (2014). Link PDF

Turner RA, Hauksson NE, Gipe JH, Lokey RS. Selective, On-Resin N-Methylation of Peptide N-Trifluoroacetamides. Org. Lett. 15 (2013) 5012-5015. Link PDF

Jacobson MP, Lokey RS, Liras S, Liras J. Designing Molecules to Cross Biological Membranes. Curr. Top. Med. Chem. 13, (2013) 775. Link

Woehrmann MH, Bray WM, Durbin JK, Nisam SC, Michael AK, Glassey E, Stuart JM, Lokey RS. Large-scale cytological profiling for functional analysis of bioactive compounds. Mol. BioSyst. 9, (2013) 2604-2617. Link PDF

Bockus AT, McEwen CM, Lokey RS. Form and Function in Cyclic Peptide Natural Products: A Pharmacokinetic Perspective. Curr. Top. Med. Chem.. 13, (2013) 821-836. PMID: 23578026. Link PDF

Rand AC, Leung SSF, Eng H, Rotter CJ, Sharma R, Kalgutkar AS, Zhang Y, Varma MV, Farley KA, Khunte B, Limberakis C, Price DA, Liras S, Mathiowetz AM, Jacobson MP, Lokey RS. Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance. MedChemComm. Web Publication 16 Aug 2012. Link

Zuckerman NB, Myers AS, Quan TK, Bray WM, Lokey RS, Hartzog GA, Konopelski JP. Structural determination of NSC 670224, synthesis of analogues and biological evaluation. ChemMedChem. 7, (2012) 761-765. PMID: 22378491. Link

Johnson TA, Sohn J, Inman WD, Samarkand AE, Loveridge ST, Vervoort HC, Tenney K, Liu J, Ang KKH, Ratnam J, Bray WM, Gassner NC, Shen YY, Lokey RS, McKerrow JH, Boundy-Mills K, Nukanto A, Kanti A, Julistiono H, Kardono LBS, Bjeldanes LF, Crews P. Natural product libraries to accelerate the high-throughput discovery of therapeutic leads. J. Nat. Prod. 74, (2011) 2545-2555. PMID: 22129061. Link

Peach KC, Bray WM, Shikuma NJ, Gassner NC, Lokey RS, Yildiz FH, Linington RG. An image-based 384-well high-throughput screening method for the discovery of biofilm inhibitors in Vibrio cholerae. Mol. Biosyst. 4, (2011) 1176-1184. PMID: 21246108. Link

White TA, Renzelman CM, Rand AC, Rezai T, McEwen CM, Gelev VM, Turner RA, Linington RG, Leung SSF, Kalgutkar AS, Bauman JN, Zhang Y, Liras S, Price DA, Mathiowetz AM, Jacobson MP, Lokey RS. On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds. Nat. Chem. Biol. 7, (2011) 810-817. PMID: 21946276. PMCID; PMC3210067. Link

Watts KR, Morinaka BI, Amagata T, Robinson SJ, Tenney K, Bray WM, Gassner NC, Lokey RS, Media J, Valeriots FA, Crews P. Biostructural features of additional jasplakinolide (jaspamide) analogues. J Nat Prod. 74, (2011) 341-351. PMID: 21241058. Link

Tamble CM, St. Onge RP, Giaever G, Nislow C, Williams AG, Stuart JM, Lokey RS. The synthetic genetic interaction network reveals small molecules that target specific pathways in Sacchromyces cerevisiae. Mol. Biosyst. 7, (2011) 2019-2030. PMID: 21487606. Link

Kapitzky L, Beltrao P, Berens TJ, Gassner N, Zhou C, Wüster A, Wu J, Babu MM, Elledge SJ, Toczyski D, Lokey RS, Krogan NJ. Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action. Mol. Syst. Biol. 6, (2010) 1-14. PMID: 21179023. PMCID: PMC3018166. Link

Möller C, Melaun C, Castillo C, Diaz ME, Renzelman CM, Estrada O, Kuch U, Lokey RS, Mari F. Functional hypervariability and gene diversity of cardioactive neuropeptides. J. Biol. Chem. 285, (2010) 40673-40680. PMID: 20923766. PMCID: PMC3003366. Link

Robinson SJ, Morinaka BI, Amagata T, Tenney K, Bray WM, Gassner NC, Lokey RS, and Crews P. New Structures and Bioactivity Properties of Jasplakinolide (Jaspamide): Analogues from Marine Sponges. J. Med. Chem. 53, (2010) 1651-1661. PMID: 20121114. PMCID: PMC2848536. Link

Turner RA, Weber RJ, Lokey RS. Direct Conversion of Resin-Bound Peptides to C-Terminal Esters. Org. Lett. 12, (2010) 1852-1855. PMID: 20329782. Link

Woerhmann MH, Gassner NC, Bray WM, Stuart JM, Lokey RS. HALO384: A halo-based potency prediction algorithm for high-throughput detection of antimicrobial agents. J. Biomol. Screening. 15, (2010) 196-205. PMID: 20086209. Link

Inman WD, Bray WM, Gassner NC, Lokey RS, Tenney K, Shen YY, TenDyke K, Suh T. Crews P. A β-carboline alkaloid from the Papau New Guinea marine sponge Hyrtios reticulatus. J. Nat. Prod. 73, (2010) 255-257. PMID: 20000782. PMCID: PMC2829331. Link

Boot CM, Gassner NC, Compton JE, Tenney K, Tamble CM, Lokey RS, Holman TR, Crews P. Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen. J. Nat. Prod. 70, (2007) 1672-1675. PMID: 17929896. Link

Seballos L, Richards N, Stevens DJ, Patel M, Kapitzky L, Lokey RS, Millhauser G, Zhang JZ. Competitive binding effects on surface-enhanced Raman scattering of peptide molecules. Chem. Phys. Lett. 447, (2007) 335-339. PMID: 20648229. PMCID: PMC2905820. Link

Turner RA, Oliver AG, Lokey RS. Click Chemistry as a Macrocyclization Tool in the Solid Phase Synthesis of Small Cyclic Peptides. Org. Lett. 9, (2007) 5011-5014. PMID: 17956112. Link

Nehil MT, Tamble CM, Combs DJ, Kellogg DR, Lokey RS. Uncovering genetic relationships using small molecules that selectively target yeast cell cycle mutants. Chem. Biol. Drug Des. 69, (2007) 258-264. PMID: 17461973. Link

Schuresko LA, Lokey RS. A Practical Solid Phase Synthesis of Glu7-Phalloidin and Entry into Fluorescent F-Actin Binding Reagents. Angew. Chem. Int. Ed. 46, (2007) 3547-3549. PMID: 17385816. Link

Combs DJ, Lokey RS; Extended peptoids: a new class of oligomers based on aromatic building blocks. Tet. Lett. 48, (2007) 2679-2682. PMID: 18398447. PMCID: PMC1890040. Link

Gassner NC, Tamble CM, Bock JE, Cotton M, White KN, Tenney K, St.Onge RP, Proctor MJ, Giaever G, Davis RW, Crews, P, Holman TR, Lokey RS. Accelerating the Discovery of Biologically Active Small Molecules Using a High-Throughput Yeast Halo Assay. J. Nat. Prod. 70, (2007) 383-390. PMID: 17291044. PMCID: PMC2533267. Link

Ralifo P, Sanchez L, Gassner NC, Tenney K, Lokey RS, Holman TR, Valeriote FA, Crews P; Pyrroloacridine Alkaloids from Plakortis quasiamphiaster: Structures and Bioactivity. J. Nat. Prod. 70, (2007) 95-99. PMID: 17253856. PMCID: PMC1839848. Link

Rezai, T, Bock, JE, Vuong, Kalyanaraman K, C, Lokey RS*, Jacobson MP*. Conformational Flexibility, Internal Hydrogen Bonding, and Passive Membrane Permeability: Successful In Silico Prediction of the Relative Permeabilities of Cyclic Peptides. J. Am. Chem. Soc. 128, (2006) 14073-14080 (*Corresponding authors). PMID: 17061890. Link

Rezai T, Yu B, Millhauser GL, Jacobson MP, Lokey RS. Testing the conformational hypothesis of passive membrane permeability using synthetic cyclic peptide diastereomers. J. Am. Chem. Soc. 128, (2006) 2510-2511. PMID: 16492015. Link

Perlman ZE, Bock JE, Peterson JR, Lokey RS. Geometric Diversity Through Permutation of Backbone Configuration in Cyclic Peptide Libraries. Bioorg. Med. Chem. Lett. 15, (2005) 5329-5334. PMID: 16213707. Link

Simon RA, Schuresko L, Dendurkuri N, Goers E, Murphy B, Lokey RS. One-bead-one-compound library of end-capped dipeptides and deconvolution by microflow NMR. J. Combi. Chem. 7, (2005) 697-702. PMID: 16153064. Link

Lokey RS. Forward chemical genetics: progress and obstacles on the path to a new pharmacopoeia. Curr. Op. Chem. Biol. 7, (2003) 91-96. PMID: 12547432. Link

Peterson JR,* Lokey RS,* Mitchison TJ, Kirschner MW. A chemical inhibitor of N-WASP reveals a new mechanism for targeting protein interactions. Proc. Nat. Acad. Sci. USA. 98, (2001) 10624-10629. (*authors contributed equally). PMID: 11553809. PMCID: PMC58516. Link

Guelev VM, Cubberley MS, Murr MM, Lokey RS, Iverson BL. Design, Synthesis and Characterization of Polyintercalating Ligands. Meth. Enzym. 340, (2001) 556-570. PMID: 11494870. Link

Guelev VM, Harting MT, Lokey RS, Iverson BL. Altered sequence specificity identified from a library of DNA-binding small molecules. Chem. Biol. 7, (2000) 1-8. PMID: 10662682. Link

Lokey RS, Kwok Y, Guelev V, Pursell C, Hurley LH, Iverson BL. A new class of polyintercalating molecules. J. Am. Chem. Soc. 119, (1997) 7202-7210. Link.

Lokey RS, Iverson BL. Synthetic molecules that fold into a pleated secondary structure in solution. Nature 375, (1995) 303-305. Link

Lokey RS, Mills NS. A sandwich complex containing trimethylenemethane. Organometallics 8, (1989) 1803-1805. Link