C Chemistry

**** ***** ****** *********@*********.***

Eugene, OR 97404 Home 541-***-**** Cell 510-***-****

ORGANIC, MEDICINAL, PEPTIDE, & PROCESS CHEMIST

A synthetic organic chemist with a M.S. degree and over 15 years industrial research experience in:

Fluorescent dye synthesis,

Hetero-bifunctional crosslinker synthesis and bioconjugation chemistry,

Synthesis of silanes & - reactive PEGylated thiols for surface chemistry & materials science,

Medicinal chemistry research - structure based drug design,

Peptide chemistry, and

Process chemistry.

SIGNIFICANT ACCOMPLISHMENTS

Wrote an original research proposal and independently worked on the proposals resulting in the discovery of hepta- and hexa-peptide inhibitors of the C5a receptor resulting in two patents.

Made key observations, discoveries, and contributions that allowed the successful manufacture of ELND004 on > 200 kg scale.

Discovered alternate crystallization conditions allowing for the crystallization of ELND001 as a single polymorph.

EXPERIENCE

LIFE TECHNOLOGIES, Eugene, OR 08/2011-Present

Organic Production

Scientist III

Manufactured fluorescent dyes (Fluoresceins, Rhodamines, Alexa Fluors, BODIPYs, and more), linkers, and conjugates from a portfolio of OVER 3000 marketed products in ISO9001 and ISO13485 environments according to production deadlines.

Performed troubleshooting of problematic syntheses.

Participated in the creation of a cGMP certified scale-up synthesis lab. Performed guard band studies for the process validation.

ELAN PHARMACEUTICALS, INC., South San Francisco, CA 12/2003-02/2011

Process Chemistry

(2007-2011) Scientist

(2003-2007) Associate Scientist (Ph.D. entry level)

Responsible for the scale-up synthesis of lead compounds for toxicology studies and route improvement & process optimization for clinical candidates.

Stream-lined the synthesis of ELND004, a small molecule integrin binding inhibitor. Eliminated one step and two chromatographic purifications. A successful GMP manufacturing campaign (>200 kg) resulted from these contributions.

Wrote synthetic procedures, assembled data packages, provided reference samples and advanced intermediates for technology transfers to external contract manufacturing organizations (CMOs).

Participated in the technology transfers of Elan Development compounds, ELND007 and ELND004 to CMOs.

ZYOMYX, INC., Hayward, CA 06/1999-09/2003

Organic Chemistry

(2000-2003) Associate Scientist

(1999-2000) Senior Research Associate

Synthesized organic surface coating agents to crosslink biomolecules, proteins, or other organic compounds to glass slides and micro-chips of silicon oxide, titanium dioxide, and ultra-flat gold coated surfaces for the development of proteomics micro-array screening devices.

Developed new oligo-ethylene glycol containing hetero-bifunctional thiol and silane crosslinkers for the conjugation of biomolecules to microchips. Wrote protocols (SOPs) for technology transfer to CMOs.

Performed troubleshooting, process optimization, and scale-up synthesis of an aldehyde terminated trialkoxysilane. Increased purity from 26% to 99% and doubled the mass yield.

Recruited, hired, and supervised research associates (M.S. and B.S. level). Managed three direct reports.

EPIX MEDICAL, INC., Cambridge, MA 05/1998-01/1999

Medicinal Chemistry

Senior Research Associate,

Synthesized analogs of a gadolinium chelator, diethylenetriaminepentaacetic acid (DTPA) for use in MRI contrasting agents.

Performed organic synthesis of intermediates of Schering AG's MRI contrasting agent, Gadomer 17.

EISAI RESEARCH INSTITUTE, Andover, MA 01/1996-04/1998

Medicinal Chemistry

Researcher II

Performed the multi-step synthesis of the C1-C13 fragment of Halichondrin B, an anti-cancer, Tubulin-binding carbohydrate natural product in 17 steps to prepare 8 grams. Also synthesized 186 grams of an intermediate after 4 steps.

Synthesized Janssen's anti-cancer Ras inhibitor.

Synthesized analogs of Farnesyl-CVIM and Farnesyl-CVFM tetrapeptides.

UNIVERSITY OF NEBRASKA – LINCOLN, Lincoln, NE 05/1992-01/1996

Graduate Student Organic Chemistry, (M.S.)

Thesis: Enantioselective Diels-Alder Reactions: The Use of Bisoxazoline Ligands

Synthesized ten novel 1,4-bisoxazoline ligands for the formation of chiral Lewis acids catalysts for enantioselective Diels-Alder reactions. Performed over 100 catalytic, enantioselective, room temperature Diels-Alder reactions.

Improved the synthesis of the ligands by reducing the number of steps in the synthesis by two, increased the yields & purities and reduced the synthesis times by several days.

COLORADO STATE UNIVERSITY, Fort Collins, CO 01/1991-04/1992

Graduate Student Organic Chemistry

Synthesized bicyclic lactams for stereoselective dialkylation of carbonyls.

ABBOTT LABORATORIES, North Chicago, IL 04/1985-01/1991

Medicinal Chemist/Peptide Chemist

(1988-1991) Associate Chemist

(1985-1988) Research Technician

Performed structure based drug design of inhibitors of a 7TM (G-Protein Coupled) receptor, the Complement C5a receptor.

Performed peptide synthesis using solution and automated solid phase peptide synthesis.

Prepared unnatural amino acids by the Bucherer-Bergs and Arndt-Eistert reactions.

Wrote an original research proposal.

Synthesized compounds according to my proposal resulting in the successful size reduction of the lead peptide by two amino acids while simultaneously maintaining full binding potency, stabilizing the peptide against proteolytic degradation, and converting the compound to a partial agonist. Two patents, US Patents 5,387,671 and 5,386,011 were obtained as a direct result of my original ideas and work.

EDUCATION

M.S. Organic Chemistry, University of Nebraska – Lincoln, Lincoln, NE

Thesis: Enantioselective Diels-Alder Reactions: The Use of Bisoxazoline Ligands

B.S. Chemistry: Professional Degree, University of Idaho, Moscow, ID

Performed the multi-step synthesis of 4-chloromethyl-3,5-dimethyl isoxazole.

Synthesized novel 4-isoxazolyl-1,4-dihydropyridine calcium channel blockers.

PATENT APPLICATION

Ronald Cicero, Jonathan Forman, Peter Kernen, Hongbo Lu, David Quincy, Stefan Schweizer, and Peter Wagner; “Methods and Reagents for Surface Functionalization to Prepare Protein Microarrays,” U. S. Patent Application Publication, 2005, US 200-***-**** A1 and PCT Int. Appl., 2004, WO 200-***-****.

PUBLICATIONS

Y.-Z. Xu, J. L. Smith, C. M. Semko, K. I. Rossiter, J. Y. Fukuda, M. S. Dappen, D. A. Quincy, A. W. Konradi, W. Mao, B. Welch, M. Dreyer, B. Samant, H. Zhang, J. Lugar, Z. Liao, C. Henschel, E. Petersen, C. Vandevert, M. Shoemaker, N. Wehner, L. Mutter, G. Shopp, M. Krimm, L. Chen, B. Wipke, L. Dofiles, I. Gallager, J.-M. Sauer, E. K. Messersmith, M. A. Pleiss, F. Bard, T. A. Yednock, “Orally Available and Efficacious α4β1/α4β7 Integrin Inhibitors,” Bioorg. Med. Chem. Lett., 2013, 23, 4370-4373.

J. L. Smith, K. I. Rossiter, C. M. Semko, Y.-Z. Xu, D. A. Quincy, J. Jagodzinski, M. S. Dappen, A. W. Konradi, C.Vandevert, C. Garrido, W. Mao, F. B. San Pablo, B. Wipke, L. Dofiles, A. Wadsworth, E. Petersen, C. Lorenzana, S. Simmonds, E. K. Messersmith, M. A. Pleiss, F. Bard, T. A. Yednock, “PEG Conjugates of Potent α4 Integrin Inhibitors, Maintaining Sustained Levels and Bioactivity in vivo, Following Subcutaneous Administration,” Bioorg. Med. Chem. Lett., 2013, 23, 4117-4119.

G. Probst, D. L. Aubele, S. Bowers, D. Dressen, A. W. Garofalo, R. K. Hom, A. W. Konradi, J. L. Marugg, M. N. Mattson, M. L. Neitzel, C. M. Semko, H. L. Sham, J. L. Smith, M. Sun, A. P. Troung, X. M. Ye, Y.-Z. Xu, M. S. Dappen, J. Jagodzinski, P. S. Keim, P. Peterson, L. H. Latimer, D. Quincy, J. Wu, E. Goldbach, D. K. Ness, K. P. Quinn, J.-M. Sauer, K. Wong, H. Zhang, W. Zmolek, E. f. Brigham, D. Kholodenko, K. Hu, G. T. Kwong, M. Lee, A, Liao, R. N Motter, P. Sacayon, P. Santiago, C. Willits, F. Bard, M. P. Bova, S. S. Hemphill, L. Nguyen, L. Ruslim, K. Tanaka, P. Tanaka, W. Wallace, T. A Yednock, and G. S. Basi, “Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2Hpyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch,” J. Med. Chem., 2013, 56, 5261-5274.

Victoria Hulubei, Scott B. Meikrantz, David A. Quincy, Tina Houle, John I. McKenna, Mark E. Rogers, Scott Steiger, Natale, N. R., “4-Isoxazolyl-1,4-dihydropyridines Exhibit Binding at the Multidrug-Resistance Transporter,” Bioorg. Med. Chem., 2012, 20, 6613-6620.

S. Bowers, A. P. Truong, R. J. Neitz, R. K. Hom, J. M. Sealy, G. D. Probst, D. Quincy, B. Peterson, W. Chan, R. A. Galemmo, Jr., A. W. Konradi, H. L. Sham, G. Toth, H. Pan, M. Lin, N. Yao, D. R. Artis, H. Zhang, L. Chen, M. Dreyer, B. Sumant, W. Zmolek, K. Wong C. Lorentzen, E. Goldbach, G. Tonn, K. P. Quinn, J.-M. Sauer, S. Wright, K. Powell, L. Ruslim, Z. Ren, F. Bard, T. A. Yednock, and I. Griswold-Prenner,“Design and Synthesis of Brain Penetrant Selective JNK Inhibitors with Improved Pharmacokinetic Properties for the Prevention of Neurodegeneration,” Bioorg. Med. Chem. Lett., 2011, 21, 5521-5527.

J. J. Jagodzinski, D. L. Aubele, D. A. Quincy, M. S. Dappen, L. H. Latimer, R. K. Hom, R. A. Galemmo Jr., A. W. Konradi, and H. L. Sham; “A Facile Synthesis of Multigram Quantity of Ethyl 3-Ethylmorpholine-3-Carboxylate,” Tetrahedron Lett., 2011, 52, 2471-2472.

G. D. Probst, S. Bowers, J. M. Sealy, A. P. Troung, R. K. Hom, R. A. Galemmo Jr., A. W. Konradi, H. L. Sham, D. A. Quincy, H. Pan, N. Yao, M. Lin, G. Toth, D. R. Artis, W. Zmolek, K. Wong, A. Qin, C. Lorentzen, D. F. Nakamura, K. P. Quinn, J.-M. Sauer, K. Powell, L. Ruslim, S. Wright, D. Chereau, Z. Ren, J. P. Anderson, F. Bard, T. A. Yednock, and I. Griswold-Prenner; “Highly Selective c-Jun N-Terminal Kinase (JNK) 2 and 3 Inhibitors with In-Vitro CNS-Like Pharmacokinetic Properties Prevent Neurodegeneration,” Bioorg. Med. Chem. Lett., 2011, 21, 315-319.

M. N. Mattson, M. L. Neitzel, D. A. Quincy, C. M. Semko, A. W. Garofalo, P. S. Keim, A. W. Konradi, M. A. Pleiss, H. L. Sham, E. F. Brigham, E. G. Goldbach, H. Zhang, J.-M. Sauer, and G. S. Basi; “Discovery of Sulfonamide-Pyrazole -Secretase Inhibitors,” Bioorg. Med. Chem. Lett.; 2010, 20, 2148-2150.

P. Peluso, D. S. Wilson, D. Do, H. Tran, M. Venkatasubbaiah, D. Quincy, B. Heidecker, K. Poindexter, N. Tolani, M. Phelan, K. Witte, P. Wagner, and S. Nock, "Optimizing Antibody Immobilization Strategies for the Construction of Protein Microarrays," Analytical Biochem., 2003, 312, 113-124.

M. J. Towle, K. A. Salvato, J. Budrow, B. F. Wels, G. Kuznetsov, K. K. Aalfs, S. Welsh, W. Zheng, B. M. Seletsky, M. H. Palme, G. J. Habgood, L. A. Singer, L. V. DiPietro, Y. Wang, J. J. Chen, D. A. Quincy, A. Davis, K. Yoshimatsu, Y. Kishi, M. J. Yu, and B. A. Littlefield, "In Vitro and In Vivo Anticancer Activities of Synthetic Macrocyclic Ketone Analogues of Halichondrin B," Cancer Res., 2001, 61, 1013-1021.

J. M. Takacs, D. A. Quincy, W. R. Shay, B. E. Jones, and C. R. Ross II, "Enantioselective Diels-Alder

Reactions: Novel Constrained Bis (oxazoline) Ligand-Metal Triflate Catalysts," Tetrahedron: Asymmetry, 1997, 8, 3079-3087.

J. M. Takacs, E. C. Lawson, M. J. Reno, M. A. Youngman, and D. A. Quincy, "Enantioselective Diels-Alder Reactions: Room Temperature Bis(oxazoline)-Zinc, Magnesium, and Copper Triflate Catalysts," Tetrahedron: Asymmetry, 1997, 8, 3073-3078.

M. Kawai, D. A. Quincy, B. Lane, K. W. Mollison, Y. S. Or, J. R. Luly, and G. W. Carter, "Structure-Function Studies in a Series of Carboxyl-Terminal Octapeptide Analogues of Anaphylatoxin C5a," J. Med. Chem., 1992, 35, 220-223.

M. Kawai, D. A. Quincy, B. Lane, K. W. Mollison, J. R. Luly, and G. W. Carter, "Identification and Synthesis of a Receptor Binding Site of Human Anaphylatoxin C5a," J. Med. Chem., 1991, 34, 2068-2071.

L. Schlicksupp, D. A. Quincy, and N. R. Natale, "Structure of Ethyl 2-Chloro-4-methyl-6-(1-pyrrolidinyl)

Benzoate," Acta Cryst., 1989, C45, 1561-1563.

G. Knerr, J. I. McKenna, D. A. Quincy, and N. R. Natale, "The Mass Spectral Fragmentation of Isoxazolyldihydropyridines," J. Heterocyclic Chem., 1987, 24, 1429-1433.

K. Dean Bowles, D. A. Quincy, J. I. McKenna, and N. R. Natale, "Selective Oxidation in the Presence of a Heterocycle," J. Chem. Educ., 1986, 63, 358-360.

C. K. Schauer, O. P. Anderson, N. R. Natale, and D. A. Quincy, "Structure of Diethyl 2,6-Dimethyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate, a Calcium Antagonist," Acta Cryst., 1986, C42, 884-886.

K. Dean Bowles, D. A. Quincy, B. Mallet, J. I. McKenna, and N. R. Natale, "Heterocycles and Reactive

Intermediates in the Undergraduate Organic Lab," J. Chem. Educ., 1985, 62, 1118-1120.

N. R. Natale and D. A. Quincy, "Neutral Dichromate Oxidations, Preparation and Utility of Isoxazole

Aldehydes," Synth. Commun., 1983, 13, 812-822.

PRESENTATIONS

(Presenter in bold)

N. R. Natale, H. D. Beall, V. Hulubei, A. K. Kearns, S. B. Mekrantz, D. A. Quincy, and S. Steiger, “Heteroaryl-dihydropyridines Inhibit the Multidrug Resistance Transporter,” 23rd Rocky Mountain Regional Meeting of the American Chemical Society; Westminster, CO; October 17-20, 2012; Abstract RMRM-176.

S. Steiger, D. A. Quincy, V. Hulubei, S. B. Meikrantz, and N. R. Natale, “4-Isoxazolyl-1,4-dihydropyridines Used as Inhibitors for Multidrug Resistance Transporters,” 67th Northwest Regional Meeting of the American Chemical Society; Boise, ID; June 24-27, 2012; Abstract NORM-4.

B. Brigham, A. Liao, M. Bova, K. S. Chen, C. Cabrera, X.-H. Chen, T. Cole, T. Eichenbaum, E. Goldbach, K. Hu, P. Keim, A. Konradi, M. Lee, H. Ni, L. Nguyen, M. N. Mattson, L. Mutter, D. Quincy, P. Santiago, J.-M. Sauer, G. Schopp, F. Soriano, S. Webb, N. Wehner, and G. Basi; “Treatement with a Novel Sulfonamide Gamma-Secretase Inhibitor Reduces Beta-Amyloid Production without Effects on Notch Related Toxicity in Wildtype Mice,” Neuroscience National Meeting, November 5, 2007, abstract 486.13/X7.

S. Schweizer, D.Quincy, C. Dentinger, P.Kernen, P. Wagner, and A. Acharya, “Construction of self-assembled monolayers using the Staudinger Ligation,” 228th ACS National Meeting; Philadelphia, PA; August 22-26, 2004; abstract COLL-125.

S. Schweizer, D. Quincy, R. Cicero, P. Kernen, P. Wagner, J. McFarland, J. Huang, W. Khu, S. McManus-Munoz, H. Tran, and C. Dentinger, "Synthesis and Evaluation of Bioreactive Pegylated Thiols and Disulfides for the Formation of Monolayers on Gold," 224th ACS National Meeting, August 18-22, 2002; abstract COLL-187.

H. Tran, M. Chen, H. Lu, A. Neurauter, S. McManus-Munoz, D. Quincy, J. Huang, T. Langenbacher, D. Do, P. Peluso, P. Kernen, S. Nock, and P. Wagner, "Biotin-reactive Surfaces Based on -substituted Alkanethiols on Au(111)," AVS 48th International Symposium, October 28-November 2, 2001; abstract BI-MoP6.

J. E. Forman, L. Gamble, R. S. Gascon, J. I. Henderson, D. A. Quincy, A. S. Suseno, M. -C. Tran, and

P. Wagner, "Substrate Development for Enhanced Performance of Spotted Oligonucleotide Arrays," PittCon 2001, March 4-9, 2001; abstract 684.

W. Zheng, B. M. Seletsky, M. H. Palme, G. J. Habgood, L. A. Singer, L. V. DiPietro, J. J. Chen, D. A. Quincy, M. J. Towle, K. A. Salvato, J. Budrow, B. Wels, G. Kuznetsov, K. K. Aalfs, S. Welsh, B. A. Littlefield, and M. J. Yu, "Synthetic Macrocyclic Ketone Analogs of Halichondrin B: Structure-Activity Relationships," 91st American Association for Cancer Research (AACR) Annual Meeting, April 1-5, 2000.

M. J. Towle, K. A. Salvato, J. Budrow, B. Wels, G. Kuznetsov, K. K. Aalfs, S. Welsh, W. Zheng, B. M.

Seletsky, M. H. Palme, G. J. Habgood, L. A. Singer, L. V. DiPietro, Y. Wang, J. J. Chen, D. A. Quincy, K. Yoshimatsu, M. J. Yu, and B. Littlefield, "Highly Potent In Vitro and In Vivo Anticancer Activities of Synthetic Macrocyclic Ketone Analogs of Halichondrin B," 91st American Association for Cancer Research (AACR) Annual Meeting, April 1-5, 2000.

J. R. Jeitler, T. T. Wixon, D. A. Quincy, J. I. McKenna, B. J. Lefler, Y. R. Mirzaei, R. B. Palmer, S. B.

Meikrantz, K. Nelson, T. N. Balasubramaniam, and N. R. Natale, "A Century of the Hantzsch Pyridine

Synthesis: The Value of This Venerable Process Continues to Appreciate," 219th ACS National Meeting, March 26-30, 2000, abstract CHED-104.

D. A. Quincy, "MS-325, an Albumin Targeted Contrast Agent for MRI," invited seminar at the University of Idaho, September 17, 1998.

D. A. Quincy, E. C. Lawson, W. R. Shay, B. E. Jones, and J. M. Takacs, "Catalytic Enantioselective Diels-Alder Reactions Mediated by Chiral Metal Complexes," 29th ACS Midwest Regional Meeting, November 2-5, 1994, abstract 65.

M. Kawai, D. A. Quincy, K. W. Mollison, B. C. Lane, G. W. Carter, and J. R. Luly, "Modifications of Amide Bonds in a Series of C5a-Related Hexapeptides," 208th ACS National Meeting, August 21-25, 1994, abstract MEDI-119.

J. M. Takacs and D. A. Quincy, "Enantioselective Diels-Alder Reactions via Lewis Acid Catalysts Designed for Specific Metal Ions," 103rd Nebraska Academy of Sciences Annual Meeting, April 16-17, 1993.

J. M. Takacs and D. A. Quincy, "Enantioselective Catalysis: Chiral Metal Ion Coordination Complexes as Lewis Acid Catalysts," 205th ACS National Meeting, March 28-April 2, 1993; abstract ORGN-265.

M. Kawai, D. A. Quincy, K. W. Mollison, B. C. Lane, G. W. Carter, and J. R. Luly, "Potent C5a-Related

Hexapeptides," 202nd ACS National Meeting, August 25, 1991; abstract MEDI-167.

M. Kawai, D. A. Quincy, B. Lane, K. W. Mollison, J. R. Luly, and G. W. Carter, "Structure-Function Studies in a Series of Carboxyl Terminal Octapeptide Analogs of the Fifth Component of Complement Cleavage Product, C5a," 22nd National Medicinal Chemistry Symposium; Austin, TX, July 29, 1990.

M. Kawai, D. A. Quincy, B. Lane, K. W. Mollison, J. R. Luly, and G. W. Carter, "Identification of a Receptor Binding Region of the Human Anaphylatoxin, C5a," 199th ACS National Meeting, April 22-27, 1990; abstract MEDI-87.

L. Schlicksupp, D. A. Quincy, M. L. Borth, and N. R. Natale, "Application of X-Ray Crystallography and CP-MAS to Problems in Isoxazole Chemistry," 41st ACS Northwest Regional Meeting, June 16-18, 1986; abstract 127.

N. R. Natale, D. A. Quincy, J. I. McKenna, C. S. Niou, O. P. Anderson, and C. K. Schauer, "A Facile Synthesis of Isoxazole Derivatives," 188th ACS National Meeting, August 26-31, 1984, abstract ORGN-122.

D. A. Quincy, K. Dean Bowles, N. R. Natale, O. P. Anderson, and C. K. Schauer, "Synthesis and Structure of Isoxazolyl Dihydropyridines," 39th ACS Northwest Regional Meeting, June 13-15, 1984, abstract 060.

D. A. Quincy, K. Dean Bowles, N. R. Natale, O. P. Anderson, and C. K. Schauer, "Synthesis and Structure of Isoxazolyl Dihydropyridines," 26th Idaho Academy of Sciences Meeting, April 13-14, 1984, abstract C-8.

N. R. Natale, E. C. Beedle, E. J. Evain, B. E. Marron, D. A. Quincy, J. Johnson, and J. D. Hendrix, "Lanthanide Solutions to Problems in Heterocyclic Chemistry," 2nd IUPAC Symposium on Organometallic Chemistry Directed Towards Organic Synthesis, August 28-September 2, 1983, Dijon, France, abstract Sm-01.

D. A. Quincy and N. R. Natale, "Synthesis of Isoxazole Dihydropyridines," 25th Idaho Academy of Sciences Meeting, April 15-16, 1983, abstract C-4.

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