Brian McNaughton Resume

Brian R. McNaughton, Ph. D. SUMMARY Strong record of directing a diverse and productive research program in biochemistry, biologics drug discovery, and molecular biology. Specific expertise includes protein evolution/engineering, intracellular biologics delivery, nanobodybased immunotherapeutic discovery, RNA-targeted protein and peptide drug discovery, protein-based cancer imaging, antiviral entry inhibitor discovery, synthetic organic chemistry and biocatalysis / artificial metalloenzyme discovery and optimization. Strong record of teaching undergraduate and graduate level chemistry, chemical biology, and biological sciences courses. Recipient of college-wide award for teaching and mentoring at the undergraduate level.

EXPERIENCE DELAWARE STATE UNIVERSITY - 2020-CURRENT § Senior Fellow – Delaware Institute for Science & Technology § Adjunct Professor – Department of Biological Sciences

COLORADO STATE UNIVERSITY - 2015-18 § Associate Professor of Chemistry (primary affiliation) § Associate Professor of Biochemistry & Molecular Biology (secondary affiliation)

COLORADO STATE UNIVERSITY - 2009-15 § Assistant Professor of Chemistry (primary affiliation) § Assistant Professor of Biochemistry & Molecular Biology (secondary affiliation)

HARVARD UNIVERSITY - 2007-09 § Postdoctoral Fellow, Advisor: Professor David R. Liu

UNIVERSITY OF ROCHESTER - 2002-07 § Graduate Student, Advisor: Professor Benjamin L. Miller

EDUCATION UNIVERSITY OF ROCHESTER

INDIANA UNIVERSITY OF PENNSYLVANIA

2002-2007 Doctor of Philosophy, Chemistry (Chemical Biology)

1996-2000 Bachelor of Science, Chemistry

TEACHING ▪ CHEM 341: Modern Organic Chemistry I (CSU) ▪ CHEM 543: Physical Organic Chemistry (CSU) ▪ CHEM 521: Principles of Chemical Biology (CSU) ▪ CHEM 523: Methods in Chemical Biology (CSU)

▪ BIOL 420: Immunology (DSU) ▪ BIOL 215: Cell Biology Laboratory (DSU) ▪ BIOL 415: Pharmacology (DSU) ▪ BIOL 310: Molecular Biology (DSU) ▪ BIOL 101: General Biology (DSU)

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PUBLICATIONS As principal investigator – *corresponding author; (undergraduate co-author) 1.

WZ Charles, CR Fairies, YT Street, AD Wilson, DW Crawford, PC Beardslee, A Hendrickson, BR McNaughton* “Cell Surface β-Lactamase Recruitment as a Selection Platform to Identify Macromolecular Interactions” (in preparation) 2. I Hassan, J Fuller, V Dippon, AN Ta, MW Dannerman, BR McNaughton*, A Alexandrova*, T Rovis* “Tuning Through-Space Interactions via the Secondary Coordination Sphere of an Artificial Metalloenzyme Leads to Enhanced Rh(III)-Catalysis” Chemical Science, 13, 9220 (2022) 3. WZ Charles, CR Faries, YT Street, LS Flowers BR McNaughton* “Antibody Recruitment as a Therapeutic Strategy: A Brief History and Recent Advances” ChemBioChem, 23, e202200092 (2022) 4. PA Rosario, BR McNaughton* “Computational Hot-Spot Analysis of the SARS-CoV-2 Receptor Binding Domain / ACE2 Complex” ChemBioChem, 22, 1196 (2021) 5. AN Ta, RL Tennyson, DC Aceveda, BR McNaughton* “Disparities Between Antibody Occupancy, Orientation, and Cytoxicity in Immunotherapy” ChemBioChem, 21, 2435 (2020) 6. T Ikeda, RL Tennyson, SN Walker, RS Harris, BR McNaughton* “Evolved Proteins Inhibit Entry of Enfuvirtide-Resistant HIV-1” ACS Infectious Diseases, 5, 634 (2019) 7. IS Hassan, AN Ta, MW Danneman, N Semakul, M. Burns, CH Basch, VN Dippon, BR McNaughton*, T Rovis* “Asymmetric δ-Lactam Synthesis with a Monomeric Streptavidin Artificial Metalloenzyme” J. Am. Chem. Soc., 141, 4815 (2019) 8. J Jenkins, DW Crawford, CE Cavender, DH Mathews, BR McNaughton*, JE Wedekind* “Structure of HIV TAR in Complex with a Lab-Evolved RRM Provides Insight into Duplex RNA Recognition and Synthesis of a Constrained Peptide that Impairs Transcription” Nucleic Acids Research, 45, 6401 (2018) 9. JN Bjerke, PC Beardslee, BR McNaughton* “Recent Advances in CRISPR Base Editing: From A to RNA” Biochemistry, 57, 6, 886 (2018) 10. KG Nottingham, A McNally*, BR McNaughton* “Synthesis of Biotinylated Diazinon: Lessons Learned for Biotinylation of Thiphosphate Esters” Tetrahedron Letters, 59, 234 (2018) 11. SN Walker, RL Tennyson, T Ikeda, RS Harris, BR McNaughton* “Evaluation of Sequence Variability in HIV-1 gp41 C-peptide Helix-Grafted Proteins” Bioorganic & Medicinal Chemistry, 26, 1220 (2018) 12. VJ Bruce, BR McNaughton* “Inside Job: Methods for Delivering Exogenous Proteins to Mammalian Cells” Cell Chemical Biology, 24, 924 (2017) 13. Z Zhou, G Vaidyanathan, D McDonald, C Mo Kang, I Balyasnikova, N Devoogdt, AN Ta, BR McNaughton, M Zalutsky* “Fluorine-18 Labeling of the HER2-Targeting Sncle-Domain Antibody 2RS15d Using a Residualizing Label and Preclinical Evaluation” Molecular Imaging and Biology, 19, 867 (2017) 14. AN Ta, BR McNaughton* “Antibody and Antibody Mimetic Immunotherapeutics” Future Medicinal Chemistry, 9, 1301 (2017) 15. VJ Bruce, BR McNaughton* “Analysis of Nanobody-Conjugates and Protein Fusions as Bioanalytical Reagents” Analytical Chemistry, 89, 3819 (2017) 16. VJ Bruce, AN Ta, BR McNaughton* “Minimalist Antibodies and Mimetics: An Update and Recent Applications” ChemBioChem, 17, 1892 (2016) 17. RL Tennyson, SN Walker, T Ikeda, RS Harris, AJ Kennan*, BR McNaughton* “Helix-Grafted Pleckstrin Homology Domains Suppress HIV-1 Infection of CD4-Positive Cells” ChemBioChem, 17, 1945 (2016) 18. DW Crawford, BD Blakeley, P-H Chen, C Sherpa, SFJ Le Grice, IA Laird-Offringa, BR McNaughton* “An Evolved RNA Recognition Motif That Suppresses Tat/TAR-Dependent Transcription” ACS Chemical Biology, 8, 2206 (2016) 19. AM Chapman, BR McNaughton* “Scratching the Surface: Resurfacing Proteins to Endow New Properties and Function” Cell Chemical Biology, 23, 543 (2016) 20. VJ Bruce, M Lopez-Islas, BR McNaughton* “Resurfaced Cell-Penetrating Nanobodies: A Potentially General Solution for Intracellularly Targeted Protein Drug Discovery” Protein Science, 25, 1129 (2016)

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21. MA Gray, RN Tao, SM DePorter, DA Spiegel, BR McNaughton* “Nanobody Activation Immunotherapeutics That Selectively Destroys HER2-Positive Breast Cancer Cells” ChemBioChem, 17, 155 (2016) 22. AM Chapman, BR McNaughton* “Synthetic Proteins That Bind the Oncoprotein Gankyrin, Disrupt Its Interaction with S6 ATPase, and Suppress MDM2/Gankyrin-Dependent Polyubiquitination of p53” ACS Chemical Biology, 10, 1880 (2015) 23. SN Walker, AM Chapman, RL Tennyson, AJ Kennan*, BR McNaughton* “GLUE That Sticks to HIV: A HelixGrafted GLUE Protein That Potently and Selectively Binds HIV gp41 N-terminal Helical Region” ChemBioChem, 16, 219 (2015) 24. AM Chapman, BE Rogers, BR McNaughton* “Characterization of the Binding Interaction Between the Oncoprotein Gankyrin and Grafted S6 ATPase” Biochemistry, 53, 6857 (2014) 25. AM Chapman, BR McNaughton* “A Synthetic Protein that Binds the Oncoprotein Gankyrin and Inhibits Gankyrin-Dependent Oncogenic Cellular Events” ACS Chemical Biology, 9, 2223 (2014) 26. SM DePorter, BR McNaughton* “Engineered Bacteriophage as Nanocarriers for the Delivery of Exogenous Imaging Proteins and Enzymes to Human Prostate Cancer Cells” Bioconjugate Chemistry, 25, 1620 (2014) 27. U Mohan, R Burai, BR McNaughton* “Reactivity Between Acetone and Single-Stranded DNA Containing a 5¢Capped 2¢-Fluoro-N7-Methyl Guanine” Tetrahedron Letters, 55, 3358 (2014) 28. BD Blakeley, BR McNaughton* “Synthetic RNA Recognition Motifs that Selectively Bind HIV-1 TransActivation Response Element Hairpin RNA” ACS Chemical Biology, 9, 1320 (2014) 29. SM DePorter, I Lui, VJ Bruce, MA Gray, M Lopez-Islas, BR McNaughton* “Mutational Effects Modulate the Efficiency, Cell-Selectivity, and Functional Enzyme Delivery of a Protein Transduction Domain” Molecular BioSystems 4, 10 (2014).

30. BD Blakeley, J Shattuck, MB Coates, E Tran, I Laird-Offringa, BR McNaughton* “Analysis of Protein/RNA Complexes Involving an RNA Recognition Motif Engineered to Bind Hairpins with 7- and 8-Nucleotide Loops” Biochemistry 52, 4754 (2013).

31. U Mohan, R Burai, BR McNaughton* "In Vitro Evolution of a Friedel-Crafts Deoxyribozyme" Organic & Biomolecular Chemistry 11, 2241 (2013) 32. SM DePorter, I Lui, U Mohan, BR McNaughton* "A Protein Transduction Domain with Cell Uptake and Selectivity Profiles that are Controlled by Multivalency Effects" Chemistry & Biology 20, 434 (2013).

33. SM DePorter, NK Hendricks, MA Gray, BR McNaughton* "A One-Pot Synthesis of Micron-sized and Nanoscale poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) particles" Tetrahedron Letters 53, 6436 (2012) 34. SM DePorter, I Lui, BR McNaughton* "Programmed Cell Adhesion and Growth on Cell-Imprinted Polyacrylamide Hydrogels" Soft Matter 8, 10403 (2012) 35. BD Blakeley, SM DePorter, U Mohan, R Burai, BS Tolbert, BR McNaughton* "Methods for Identifying and Characterizing Interactions Involving RNA" Tetrahedron 68, 8837 (2012) 36. BD Blakeley, AM Chapman, BR McNaughton* "Split-Superpositive GFP Reassembly is a Fast, Efficient, and Robust Methods for Detecting Protein-Protein Interactions In Vivo" Mol. BioSystems 8, 2036 (2012).

37. R Burai, J Chatwichien, BR McNaughton* “A Programmable Build - Couple Approach to the Synthesis of Heterofunctionalized Polyvalent Molecules" Organic & Biomolecular Chemistry 9, 5056 (2011) Harvard University (postdoctoral studies) 38. JJ Cronican, DB Thompson, KT Beier, BR McNaughton, CL Cepko, DR Liu “Potent Delivery of Functional Proteins into Mammalian Cells In Vitro and In Vivo Using a Supercharged Protein” ACS Chemical Biology 5, 747 (2010) 39. BR McNaughton, JJ Cronican, DB Thompson, DR Liu “Mammalian Cell Penetration, siRNA Transfection, and DNA Transfection by Supercharged Proteins” Proc. Natl. Acad. Sci, USA 106, 6111 (2009) 40. MR Rozenman, BR McNaughton, DR Liu “Solving Chemical Problems Through the Application of Evolutionary Principles” Curr. Opin. Chem. Biol. 11, 259 (2008)

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University of Rochester (graduate studies) 41. BR McNaughton, PC Gareiss, SE Jacobs, AF Fricke, GA Scott, BL Miller “A Potent Activator of Melanogenesis Identified from Small Molecule Screening” ChemMedChem 4, 1583 (2009) 42. PC Gareiss, K Sobczak, BR McNaughton, PB Palde, CA Thornton, BL Miller “Dynamic Combinatorial Selection of Small Molecules Capable of Inhibiting the (CUG) Repeat RNA–MBNL1 Interaction in vitro: Discovery of Lead Compounds Targeting Myotonic Dystrophy (DM1)” J. Am. Chem. Soc. 130, 16254 (2008) 43. BR McNaughton, BL Miller “A Facile Synthesis of 2-Ethyl-Quinoline-3-Carboxylic Acid Hydrochloride” Org. Synth. 85, 27 (2008) 44. BR McNaughton, PC Gareiss, BL Miller “Identification of a High-Affinity and Selective Ligand for the HIV-1 Frameshift-Inducing RNA Stemloop from an 11,325 Member Resin-Bound Dynamic Combinatorial Library” J. Am. Chem. Soc. 129, 11306 (2007) 45. P Palde, BR McNaughton, NT Ross, PC Gareiss, CR Mace, RC Spitale, BL Miller “Single-Step Synthesis of Functional Organic Receptors via a Tri-directional Minisci Reaction” Synthesis 15, 2287 (2007) 46. BR McNaughton, BL Miller “Resin-Bound Dynamic Combinatorial Chemistry” Org. Lett. 8, 1803 (2006) 47. BR McNaughton, KM Bucholtz, Moure, AC, BL Miller “Self-Selection in Olefin Cross-Metathesis: A Study on the Effects of Remote Functionality” Org. Lett. 7, 733 (2005 48. N Ross, BR McNaughton, BL Miller “Combinatorial Chemistry in the Drug Discovery Process” Drug Discovery Handbook, Wiley & Sons, Chapter 21 (2004) 49. BR McNaughton, BL Miller “A Mild and Efficient One-Step Synthesis of Quinolines” Org. Lett. 5, 4257 (2003)

CURRENT RESEARCH FUNDING 2022-27

2021-22

2021 2022-24

NIH – Research Centers in Minority Institutions (RCMI) “Interdisciplinary Health Equity Research (IHER) Center” Roles: PI for research project “Integrating Low-Cost Paper-Based Devices and Personalized Immunotherapeutics to Treat Triple Negative Breast Cancer” (1U54MD015959), and, Director: Investigator Development Core Delaware Biosciences Institute – Applied Research Collaborations (ARC) “Novel Immunotherapeutics Targeting PMSA-Positive Prostate Cancer” Role: PI INBRE Core Access Award Role: PI National Institutes of Health (NIGMS) “Evolved RNA Recognition Motifs for Therapeutic and Gene Editing Applications” (R15GM141783) Role: PI

$1,432,750

$75,000

$4,000 $438,000

COMPLETED RESEARCH FUNDING 2021

2017

2016 2015

Delaware-CTR ACCEL – Shovel-Ready Pilot Grants Program (ShoRe PGP) “SARSCoV-2 Entry Inhibitors as Therapeutics and Prophylaxis” Role: PI National Institutes of Health (NIGMS), “Cyclic Peptide Inhibitors of HIV-1 Proliferation” (R01GM123864) Role: co-PI Novartis, “Evolution of CUG Repeat RNA-Binding Proteins” Role: PI National Institutes of Health (NIGMS), “Protein Drug Leads That Target Challenging Protein or Nucleic Acid Structures” (R01MG107520, diversity supplement) Role: PI

4

$29,000

$1,571,690

$50,000 $21,346

2014

2014 2014 2012

2012 2010 2010

National Institutes of Health (NIGMS), “Protein Drug Leads That Target Challenging Protein or Nucleic Acid Structures” (R01MG107520) Role: PI Coca-Cola Corporation, “Low-Cost Detection of Candidatus Liberibacter” Role: PI Colorado Center for Drug Discovery, “Inhibitors of HIV Entry” Role: PI Leukemia Research Foundation, “Overcoming Resistance to Chemotherapeutic Intervention in Leukemia” Role: PI Colorado Center for Drug Discovery, “Evolution of Gankyrin-Binding Proteins” Role: PI CSURF-CSU Ventures, “SAR Analysis of Novel Anti-Flaviviral Compounds” Role: co-PI DoD/CDMPR, “A Selection-Based Approach to Evolve Prostate Cancer-Selective CellPenetrating Peptides Role: PI

5

$1,489,900

$80,000 $50,000 $100,000

$50,000 $50,000 $330,750