QIBO ZHANG, Ph.D.
Concord, OH 44077
Phone: 518-***-****
*************@*****.***
HIGHLIGHTS OF QUALIFICATIONS
Drug Development Expertise
Development of qualitative and quantitative HPLC and LCMSMS methods;
Strong understanding of the biological and organic chemistry basis of biotransformation;
o elucidate drug metabolic pathways;
In vivo and in vitro drug metabolism and biotransformation (hands-on experience):
o metabolic stability;
o metabolite profiling;
o metabolite identification;
o metabolite structure elucidation;
o metabolite generation;
o reactive metabolite identification;
o CYP inhibition;
Identify enzyme turnover products;
Investigate enzymatic reaction mechanisms;
MS/NMR and Structural Elucidation
Expert knowledge about LC-MS/MS operation and data interpretation;
Isolation and purification of metabolites from biological matrix using chromatography methods;
Structural determination by MS, MS/MS, NMR, and IR;
Determination of stereochemistry;
Expert knowledge about interpretation of 1D NMR spectra, including 1H, 13C, 19F, 31P, and 2H;
Expert knowledge about acquisition and interpretation of 2D NMR spectra, including COSY, COSY -
, TOCSY, NOESY/ROESY, HSQC/HMQC, HMBC, HSQC-TOCSY.
Instrumentation
LC-MS (Sciex single, triple Quadrupole, and QTrap, ESI, APCI, and APPI sources, Analyst software,
Waters Micromass Q-TOF2 with MassLynx software), trouble shooting and maintenance;
Analytical HPLC (Shimadzu, Waters, Agilent, Beckman-Coulter systems, including trouble-shooting);
NMR (Bruker and Varian, Topspin, Xwinnmr, IconNMR, Vnmr, WinNMR, Nuts, and Flex software);
NMR helium filling, probe changing, parameter optimizing, etc.
Prep HPLC (Waters, Shimadzu, Gilson);
UV-Visible, FPLC, CD, IR.
Qibo Zhang 1
PROFESSIONAL EXPERIENCE
Ricerca Biosciences, Concord, OH. (July 2008 – present)
Senior Scientist, Discovery Biology
Metabolite identification and structure elucidation;
Elucidate metabolic/biotransformation pathways;
Bioanalytical method developments to support PK, TK, and in vitro ADME assays;
Bioanalytical method developments via compound derivatization;
Mentor junior scientists;
Operate and troubleshoot API3200 QTrap for metabolite ID and structure elucidation (in vivo and in vitro, hot
and cold, GLP and Non-GLP);
Operate and troubleshoot API3000 and API4000 instruments;
Development of HPLC and LCMSMS methods;
Experienced with WinNonlin for Non-compartmental PK analysis;
Purification and structure determination of metabolites and impurities using NMR and mass spectroscopy;
Perform in vitro drug metabolism assays:
Phase I and Phase II metabolic stability testing using microsomes, S9, and hepatocytes; metabolite
profiling; metabolite identification; metabolite structure elucidation; reactive metabolite identification;
CYP inhibition and reaction phenotyping; plasma protein binding determination.
Novobiotic Pharmaceuticals, Cambridge, MA. (Feb. 2007–Jul. 2008)
Senior Chemist
Antibiotic discovery research;
Superuser of a Bruker 500 MHz instrument with three probes (QNP, 2.5 mm BBI, 1 mm TXI);
Structural determination of complex compounds by NMR, MS, MSMS, and IR;
Determination of stereochemistry;
Exact mass measurement using Q-TOF instrument;
Operate and maintain a Waters Micromass Q-TOF2 instrument;
Mentor junior scientists;
Identification of secondary metabolites;
Bioassay guided isolation of natural products from biological matrix using a variety of chromatography
methods;
Development of HPLC and LCMS methods;
Dereplication of known natural products;
Albany Molecular Research, Inc., Department of Metabolism & Biotransformation, Albany, NY. (2001–Feb. 2007)
Senior Research Scientist I (2003–Feb. 2007)
Senior Research Scientist (2001–2002)
Isolated and structurally characterized metabolites;
Purified and structurally elucidated complex compounds using NMR and mass spectroscopy;
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Elucidate metabolic/biotransformation pathways;
Set up and operated API 2000 triple quad LCMS system, including for quantitation;
Developed qualitative and quantitative HPLC and LCMSMS methods;
Developed and performed in vitro ADME studies;
o metabolic stability testing;
o metabolite profiling;
o metabolite identification;
o metabolite structure elucidation;
o metabolite generation;
o reactive metabolite identification;
o CYP inhibition analysis and reaction phenotyping;
o caco-2 cell permeability testing, and plasma protein binding;
Performed high throughput screening of biocatalytic reactions and optimized and scaled-up promising
reactions; The biocatalysts include commercial enzymes and microorganisms;
Identified, purified, and characterized enzymatic reaction products;
Elucidated decade-old mystery about the key 14-hydroxylation step during the biotransformation of
codeine to 14-hydroxycodeine;
Discovered a catalytic chemistry that converts codeinone to 14-hydroxycodeinone, which is a key
intermediate for the synthesis of many analgesic drugs including oxycodone (30 tons/year).
University of Minnesota, Minneapolis, MN. (1999–2000)
Postdoctoral Associate, Advisers: Hung-wen (Ben) Liu & David H. Sherman
Isolated and purified macrolide antibiotics from Streptomyces venezuelae and characterized these
compounds spectroscopically by NMR and MS.
Chemically synthesized biosynthetic precursors of anticancer agent mitomycin;
Deleted the mmcL gene from mitomycin gene cluster in Streptomyces lavendulae;
Subcloned glf gene into pET-24b vector and expressed in Escherichia coli;
Purified UDP-galactopyranose mutase from E. coli and characterized this enzyme;
Developed HPLC methods for enzyme assay;
Purified enzyme turnover products by prep HPLC and characterized these products by NMR and MS;
Designed and chemically synthesized nucleotide sugars in their less stable furanose form for enzyme
mechanistic studies;
Chemically synthesized flavin analogs and studied their properties;
Discovered and demonstrated a novel regulatory role for FAD coenzyme and provided mechanistic
insights into this unique enzymatic reaction;
Oregon State University, Department of Chemistry, Corvallis, OR. (1993–1998)
Graduate Research Assistant
Isolated and purified these metabolites by chromatography methods including prep HPLC;
Characterized these compounds spectroscopically by NMR and MS;
Qibo Zhang 3
Designed and chemically synthesized labeled precursors and potential intermediates in the biosynthesis of
blasticidin S;
Developed HPLC assays to evaluate these compounds using cell-free extract or partially purified enzymes;
Determined enzyme kinetic parameters;
Managed Streptomyces griseochromogenes to produce novel metabolites by altering fermentation
conditions;
Discovered and demonstrated blasticidin S self-resistance mechanism in S. griseochromogenes and
resistance mechanism in Streptomyces lividans;
Supervised undergraduate organic chemistry labs and graded lab reports and exams.
Beijing Medical University, College of Pharmacy, Beijing, China. (1986–1992)
Assistant Research Scientist
Isolated and characterized active components from crude extracts of Traditional Chinese Drugs using
bioassay guided screening;
Synthesized ten trimethoprim analogs for antimicrobial activity evaluation and QSAR studies.
EDUCATION
1998 Ph.D. in Organic Chemistry, Department of Chemistry, Oregon State University, Adviser: Steven J. Gould
1987 B.S. in Medicinal Chemistry, College of Pharmacy, Beijing Medical University, Beijing, China.
Graduated from high school in first place in one of ~2500 counties in the People’s Republic of China.
1982
MAJOR AWARDS
2004 AMRI Scientific Achievement Award, level 2, for opiate 14-hydroxylation project.
1989 Beijing Science and Technology Progress Award for the active component study of Chinese drug, Duhuo,
on the effects of cardiovascular system.
VISA STATUS: US Green Card Holder
REFERENCE: Available Upon Request
Qibo Zhang 4
PUBLICATIONS
Qibo Zhang,, Aaron J. Peoples, William P. Millett, Mithra T. Rothfeder, Losee Ling, Charles C. Moore. “Novoglycosylated
1.
Polyene Macrolactams with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant
Enterococci (VRE).” (in preparation)
“Novel
2. Qibo Zhang, Aaron J. Peoples, William P. Millett, Mithra T. Rothfeder, Losee Ling, Charles C. Moore.
Isofuranonaphthoquinone Produced by an Actinoplanes Strain.” J. Nat. Prod. 2009, 72, 1213-1215.
3. Aaron J. Peoples, Qibo Zhang, William P. Millett, Mithra T. Rothfeder, Brian C. Pescatore, Anne A. Madden, Losee Li ng,
Charles C. Moore. “Neocitreamicin I and II, Novel Antibiotics with Activity against Methicillin-Resistant Staphylococcus
aureus and Vancomycin-Resistant Enterococci.” J. Antibiot. 2008, 61, 457-463.
Qibo Zhang, Joseph O. Rich, Peter C. Michels, Ian C. Cotterill, and David P. Pantaleone. “14-Hydroxylation of Opiates:
4.
Catalytic Direct Autoxidation of Codeinone to 14-Hydroxycodeinone.” J. Am. Chem. Soc. 2005, 127, 7286-7287.
Zhishu Huang, Qibo Zhang, and Hung-wen Liu. “Reconstitution of UDP-galactopyranose Mutase with 1-Deaza-FAD and 5-
5.
Deaza-FAD: Analysis and Mechanistic Implications.” Bioorg. Chem. 2003, 31, 494-502.
Qibo Zhang and David H. Sherman. “Isolation and Structure Determination of Novamethymycin, a New Bioactive
6.
Metabolite of the Methymycin Biosynthetic Pathway in Streptomyces venezuelae.” J. Nat. Prod. 2001, 64, 1447-1450.
Qibo Zhang and Hung-wen Liu. “Mechanistic Investigation of UDP -galactopyranose Mutase from Escherichia coli Using 2-
7.
and 3-Fluorinated UDP-galactofuranose as Probes.” J. Am. Chem. Soc. 2001, 123, 6756-6766.
Qibo Zhang and Hung-wen Liu. “Chemical Synthesis of UDP - -L-arabinofuranose and its Turnover to UDP - -L-
8.
arabinopyranose by UDP-galactopyranose mutase.” Bioorg. Med. Chem. Lett. 2001, 11, 145-149.
Qibo Zhang, Steven J. Gould, and T. Mark Zabriskie. “Blasticidin S Resistance Mechanism in Streptomyces lividans.” In
9.
Preparation.
10. Qibo Zhang and Hung-wen Liu. “Studies of UDP-galactopyranose Mutase from Escherichia coli: An Unusual Role of
Reduced FAD in its Catalysis.” J. Am. Chem. Soc. 2000, 122, 9065-9070.
11. Qibo Zhang, Martha C. Cone, Steven J. Gould, and T. Mark Zabriskie. “Reevaluation of the Final Steps in the Biosynthesis
of Blasticidin S by Streptomyces griseochromogenes and Identification of a Novel Self-Resistance Mechanism.”
Tetrahedron, 2000, 56, 693-701.
12. Qibo Zhang. “Advanced Studies of Blasticidin S Biosynthesis.” Ph.D. Dissertation, Oregon State University, 1998.
13. Qibo Zhang, Steven J. Gould, and T. Mark Zabriskie. “A New Cytosine Glycoside from Streptomyces griseochromogenes
Produced by the in vivo Use of Enzyme Inhibitors.” J. Nat. Prod. 1998, 61, 648-651.
14. Steven J. Gould and Qibo Zhang. “Cytosinine : Pyridoxal Phosphate Tautomerase, a New Enzyme in the Blasticidin S
Biosynthetic Pathway.” J. Antibiot. 1995, 48, 652-656.
15. Laiyi Wang, Juanru Meng, Tao Wu, Rongzhi Li, Yunqing He, and Qibo Zhang. “Effects of Exogenous –Aminobutyric Acid
on Experimental Arrhythmias.” Zhongguo Yaoli Xuebao 1992, 13, 423-427.
16. Rongzhi Li, Yunqing He, Ming Chiao, Yan Xu, Qibo Zhang, Juanru Meng, Yun Gu, and Liuping Ge. “Active Constituents of
the Chinese Medicine “DUHUO” Angelica pubescens.” Yaoxue Xuebao 1989, 24, 546-551.
17. Rongzhi Li, Yunqing He, and Qibo Zhang, Juanru Meng, Laiyi Wang, and Yun Gu. “Studies of Antiarrh ythmia Constituents
-Aminobutyric Acid from Chinese Medicine “DUHUO” Angelica pubescens.” Journal of Beijing Medical University 1989,
21, 376.
18. Weizhang Zhao, Bing Yan, Qibo Zhang, and Renli Li. “Synthesis of 5-(Substituted-anilino) Uracils.” Journal of Beijing
Medical University 1989, 21, 250-251.
19. Weizhang Zhao, Renli Li, and Qibo Zhang, Ting Yu, and Yumei Cheng. “Synthesis and Antibacterial Activities of 2,4 -
Diamino-5-(Substituted-anilino) Pyrimidines.” Journal of Beijing Medical University 1988, 20, 191-194.
PATENTS
Aaron J. Peoples, Qibo Zhang, Charles M. Moore. “Glycosylated Macrolactam.” U.S. Patent#: NOV -
1.
015P2/113374.129US2. US1/Dec-020P (Provisional). (2008)
Aaron J. Peoples, Qibo Zhang, Losee Ling, Charles M. Moore “Glycosylated Polyene Macr olactam Antibiotic.” U.S.
2.
Patent#:113374. 127US1/NOV-016P1. US1/Dec-020P (Provisional). (2007)
Qibo Zhang 5
Aaron J. Peoples, Qibo Zhang, Andrew L. Staley, Losee Ling, Charles M. Moore. “Citreamicin Antibiotics with a Sugar
3.
Residue.” U.S. Patent#:113324. 127US1/NOV-013P. (Provisional). (2007)
Ian L. Scott, Dejian Xie, Joseph O. Rich, and Qibo Zhang. “Vinorelbine Derivatives and their Use as Anticancer Agents.”
4.
U.S. Provisional Patent Application No. 60/527,194, filed on December 4, 2003.
Qibo Zhang, Joseph O. Rich, Peter C. Michels, and Ian C. Cotterill. “Preparation of 14 -Hydroxylated Opiates.” U.S.
5.
Provisional Patent Application No. US 60/483,512, filed on June 27, 2003.
PRESENTATIONS
Qibo Zhang, Joseph O. Rich, Peter C. Michels, Ian C. Cotterill, and David P. Pantaleone. “Efficient preparation of 14-
1.
hydroxylated opiates from codeine.” AMRI’s Chemical Development Symposium, May 2005.
Qibo Zhang, Joseph O. Rich, Peter C. Michels, Ian C. Cotterill, and David P. Pantaleone. “Elucidation of the microbial 14 -
2.
hydroxylation of opiates and efficient preparation of 14 -hydroxylated opiates from codeine.” AMRI’s Frontiers in Drug
Discovery Symposium, October 2004.
Qibo Zhang, Joseph O. Rich, Peter C. Michels, Ian C. Cotterill, and David P. Pantaleone. “Elucidation of the microbial 14-
3.
hydroxylation of opiates and efficient preparation of 14 -hydroxylated opiates from codeine.” 228th ACS National Meeting,
August 2004.
Michael S. Hemenway, Qibo Zhang, Peter C. Michels, Joseph O. Rich, Yuri L. Khmelnitsky, Simon N. Haydar, and Bruce F.
4.
Molino. “Chemo-enzymatic Modification of Immunosuppresant Cyclosporin A.” 226th ACS National Meeting, September
2003.
Qibo Zhang and Hung-wen Liu. “Conversion of UDP -2-acetylamino-2-deoxy-galactopyranose to UDP-2-acetylamino-2-
5.
deoxy-galactofuranose by UDP-galactopyranose mutase.” 224th ACS National Meeting, August 2002.
Qibo Zhang, Yuri L. Khmelnitsky, and Peter C. Michels. “Efficient Metabolite Profiling and Production for Lead
6.
Prioritization and Expedited Drug Development.” AMRI’s Screening Symposium, April 2002.
Qibo Zhang and Hung-wen Liu. “Mechanistic Investigation of UDP -galactopyranose Mutase.” 222nd ACS National Meeting,
7.
August 2001.
Qibo Zhang and Hung-wen Liu. “Mechanistic Investigation of the Activity Enhancement of UDP -galactopyranose Mutase
8.
upon Reduction of Bound FAD.” 20th Midwest Enzyme Chemistry Conference, September 2000.
Qibo Zhang and Hung-wen Liu. “Regulation of UDP-galactopyranose Mutase Activity by Coenzyme FAD.” 20th Midwest
9.
Enzyme Chemistry Conference, September 2000.
10. Qibo Zhang, Steven J. Gould, and T. Mark Zabriskie. “A Novel Self -Resistance Mechanism Identified in the Biosynthesis of
Blasticidin S by Streptomyces griseochromogenes.” 20th Midwest Enzyme Chemistry Conference, September 2000.
11. Qibo Zhang and Hung-wen Liu. “Chemical Synthesis of Furanose Sugar Nucleotides for the Mechanistic Studies of UDP -
galactopyranose Mutase.” 220th ACS National Meeting, August 2000.
12. Qibo Zhang and Hung-wen Liu. “A Unique Role of FAD Coenzyme in UDP -galactopyranose Mutase.” Gordon Research
Conference on Enzymes, Coenzymes, and Metabolic Pathways, July 2000.
13. 2000 – Albany Molecular Research, Inc., Biocatalysis Division. “Mechanistic Studies of UDP-galactopyranose Mutase.”
14. 2000 - 220th ACS National Meeting. “Mechanistic Studies of UDP-galactopyranose Mutase.”
15. 1998 - Volcano Conference on Bioorganic Chemistry. “Studies of Blasticidin S Biosynthesis by Streptomyces
griseochromogenes.”
Qibo Zhang 6