Andrew J. Prongay, Ph.D.
Harleysville, PA 19438
*********@*****.***
Cell: 908-***-****
Home: 267-***-****
Summary
Protein Scientist with extensive experience in molecular biology and
protein chemistry (protein expression, protein purification, protein
characterization and analysis). Diverse experience includes working on
Structure Based Drug Design projects. Key member of the team that
designed the HCV NS34A protease inhibitor compound that became the drug
Victrelis. Strengths include coaching and training, experimental
creativity, data analysis and delivering information in a timely manner to
assist the efforts of team members in moving projects forward.
Technical Expertise
Generated expression construct and site-direct mutations for protein
production in bacterial, and insect cells. A limited experience with
mammalian cells. Succeeded in the expression, purification, refolding,
characterization and crystallization of more than 25 proteins of 1 mg to
700 mg scales. Technical skills include construct design, cloning, PCR,
qPCR, DNA sequencing, site-directed mutagenesis, operation of 15 - 200 L
Bioreactors, conventional and affinity liquid chromatography (IMAC, IEC,
SEC, RP, HIC, Chromatofocusing) using AKTA (Unicorn software), FPLC, HPLC
and UPLC (including Acquity H-Class Bio systems and Empower software),
electrophoresis (SDS-PAGE, isoelectric focusing, native gels, Western
blots), enzymology, enzyme assays, ligand binding measurements via TdF,
TdCD, BIAcore (SPR), ELISA, spectroscopy (UV/VIS, CD, Fluorescence),
Light Scattering (Static and Dynamic), X-ray diffraction data collection
and processing, structure determination, compound building and modeling,
lead optimization via structure based drug design, mass spectrometry (LC-MS
and LC-MS-MS) of intact proteins and peptides, peptide mapping. I have
also performed chemical modifications of proteins and thiol titrations. I
have a good understanding of ITC and DSC calorimetric methods.
Supervisory Experience
Supervised and provided extensive training of up to four scientists
concurrently with skills ranging from summer interns and recent graduates
at the technical associate level up to and including Ph.D. Principal
Scientists.
Professional Experience
AGILE-1/ALLSOURCE PPS, contract to MERCK MANUFACTURING DIVISION, Elkton, VA
2013
Senior Analytics Specialist, Technical Operation
Perform analytics in support of the manufacturing of biologics as part of
Technical Operations, including enzyme assays, ELISA assays, reagent
quantitation assays, qPCR for Residual DNA quantitation and plasmid copy
number determination, HPLC/UPLC assays of protein samples and degradation
analysis, protein quantitation assays, drafting SOPs, performing cGMP
validation assays in Quality Operations.
UNEMPLOYED and PURSUING NEW OPPORTUNITIES, 2012
Laid-off as part of a downsizing and outsourcing process following the
merger of Schering-Plough and Merck.
merck research laboratories, West Point, PA 2010-2011
Principal Scientist, Protein Science
(Relocation and position change due to the merger of Merck and Schering-
Plough.)
Supervised group of four scientists in Protein Science Department of Merck
Research Laboratories focused on generating expression constructs and
preparing proteins for ALIS screening, BioNMR and X-ray Crystallography.
Schering-Plough research Institute, Kenilworth, NJ and Cambridge, MA
1993-2010
Principal Scientist, Structural Chemistry/Protein Science, (2003-2010)
Some Key Technical Achievements:
HCV NS2 Protease:
. Designed constructs for the expression of a C-terminally truncated HCV
Genotype 2A NS2 Protease in E. coli
. Expressed, purified and refolded one of the HCV Genotype 2A NS2 Protease
constructs for ALIS screening.
. Demonstrated trans-cleavage of peptides having sequence spanning the P3
through P'6 sequence via LCMS and LC- MS-MS.
AKT3 Catalytic Domain:
. Supported drug discovery efforts with expression, purification,
characterization and crystallization of AKT3 catalytic domain. Solved
the three dimensional X-ray structure of AKT3 catalytic domain at better
than 2.0A resolution. Provided structural information on approximately
50 compounds (inhibitors) bound to AKT3 catalytic domain
HIV Integrase:
. Generated doubly and triply mutated constructs of catalytic domain and
full-length HIV Integrase, respectively.
. Expressed, purified, and characterized both constructs and crystallized
the catalytic domain construct.
. Prepared stable ternary complexes of both constructs with
oligonucleotides and inhibitors and characterized these by SEC, TdCD, TdF
and Light Scattering.
. Submitted binary complexes (Integrase and oligonucleotides) for ALIS
screening.
. Bioreactors:
. Contributed to layout design of a bacterial BioReactor Fermentation Room.
Coordinated the establishment of functional SOPs for the operation of the
BioLaffite BioReactors for high cell density growth and protein
expression.
Associate Principal Scientist, Structural Chemistry/Protein Science,
(1998-2003)
Some Key Technical Achievements:
HCV NS3-4A Protease
. Supported the drug discovery efforts of the synthetic chemistry group by
purifying and crystallizing the NS3 protease in complex with an NS4A
peptide, and by providing structural information on approximately 200
compounds (inhibitors and product analogs) bound to the HCV NS3 protease
domain.
. Key member of the team that designed Victrelis (Boceprevir/SCH503034) and
the back-up compound Narlaprevir.
Senior Scientist, Structural Chemistry/Protein Science, (1993-1998)
Some Key Technical Achievements:
IL5R:
. Purified shIL5R? and separated the isoelectric forms.
. Characterized the biochemical and biophysical properties of the shIL5R?.
. Crystallized the shIL5R? complexed with deglycosylated hIL5.
. Developed a screening assay based on the surface plasmon resonance
technology using the BIAcore.
Grb2:
. Purified the Grb2 SH2 domain, separated the intact domain from
proteolyzed fragments.
. Crystallized the Grb2 SH2 domain.
CMV Protease:
. Generated site-directed mutations of CMV protease replacing four of the
five cysteines with alanines (designated Quad3).
. Generated expression constructs of the mutated CMV protease.
. Purified the Quad3 protein.
. Chemically modified the Quad3 at Cys161 with two different mercury
compounds.
. Crystallized the derivatized and underivatized Quad3.
. Inducible Nitric Oxide Synthase.
. Identified conditions for the crystallization of human iNOS arginine
binding domain fragment using MgSO4 as a precipitant. This facilitated
the structure determination by X-ray crystallography.
. Performed spectroscopic analyses of iNOS binding to inhibitor compounds.
AWARDS
. Received the President's Award for Discovery "for Outstanding Scientific
and Technical Achievement in Discovery of an Orally Bioavailable NS3
Protease Inhibitor for Treatment of Hepatitis C Infections through
Structure Assisted Design", Schering-Plough Research Institute.
. Received the President's Award for Discovery "for Outstanding Scientific
and Technical Achievement in Protein Structures of Inducible and
Constitutive Human NO Synthases: Driving the Search for Selective
Inhibitors", Schering-Plough Research Institute.
. Received several Excellence Awards and Shining Performance Awards,
Schering-Plough Research Institute.
Education and Academic Research Experience
Purdue University, West Lafayette, IN
Post-Doctoral Research Associate, Department of Biological Sciences
(Advisor: Dr. Michael G. Rossmann)
Scholar of the American Foundation for AIDS Research, Los Angeles, CA
University of Michigan, Ann Arbor, MI
Ph.D. (Biological Chemistry) University of Michigan, Ann Arbor, MI
Thesis: Characterization of Two Active Site Mutants of Thioredoxin
Reductase from Escherichia coli.
Research Advisor: Dr. Charles H. Williams, Jr.
Dominic D. Dziewiatkowski Award in recognition of an Outstanding Ph.D.
Thesis Department of Biological Chemistry, University of Michigan
M.S., Biological Chemistry
Graduate Student Research Assistant, Department of Biological Chemistry
(Advisor: Dr. Charles H. Williams, Jr.)
Rutgers the State University of New Jersey. New Brunswick, NJ
B.S., Biology
Undergraduate Research Assistant (Advisor: Dr. Harry Brown)
Cook College, Rutgers University
Received the Joe M. Hopping Award for "Outstanding performance in
chemistry and overall educational and social excellence." Department of
Chemistry, Central Missouri State University, where I started my
undergraduate education while I was still in the United States Air Force.
Military Experience
Medical Service Specialist, United States Air Force
Performed primary emergency medical care. Honorably discharged with a rank
of Staff Sergeant, E-5.
. Receive a "Below the Zone Promotion", United States Air Force
. Selected as Hospital Outstanding Airman of the Quarter (Jan-Mar.),
United States Air Force
Patents & Pac Recommendations
1. Patent Case JB06807L01US: Factor IXa Crystals, Related Complexes and
Methods. B.M. Beyer, A.W. Hruza, R.N. Ingram, V.S. Madison, A.J. Prongay,
P. Reichert (filed on 5/7/2009, Issued 2011).
2. Patent Case JB06809L01US: Assay for PCSK9 Inhibitors. B.M. Beyer, T.
Hesson, H.V. Le, A.J. Prongay, K. Kalghatgi, J.J. Gesell, R. N. Ingram,
M.R. Ziebell (filed on 6/30/2008, issued as US 8206943 on 6/26/2012)
3. Patent Case JB06219US01: Kinase Domain polypeptide of human protein
kinase B gamma (AKT3) A.J. Prongay, T.O. Fischmann, C. Kumar, V.S.
Madison, J.E. Myers, P. Reichert, R. Syto, W.T. Windsor, L. Xiao, T. W.
Mayhood (filed 8/30/2007, issued as US 8088611 on 1/3/2012)
4. Patent Case: Kinase Inhibitors. T.Y. Chan, B.A. McKittrick, H. Pu, L.
Hong, A.J. Prongay, L. Xiao, M.A. McCoy (filed 3/28,2007; issued US
2008/0021019 A1 on 1/24/2008).
5. Patent Case: Kinase Inhibitors. T.Y. Chan, T.O. Fischmann, M.A. McCoy,
B.A. McKittrick, A.J. Prongay, H. Pu, L. Wang, L. Xiao (filed 1/24/2006,
issued as US 2008/0004257 A1).
6. Patent Case IN01154P: Macrocyclic NS-3-Serine Protease Inhibitors of
Hepatitis C Virus Comprising N-Cyclic P2 Moieties. K. X. Chen, A.
Arrasappan, S. Venkatraman, T. Parekh, H. Gu, F. G. Njoroge, V. M.
Girijavallabhan, A. K. Ganguly, A. Saksena, E. Jao, N. H. Yao, A. J.
Prongay, and V. S. Madison (filed 4/3/2001, issued as US 6,846,802 B2 on
7/25/2005).
7. Patent Case IN01155K: Macrocyclic NS-3-Serine Protease Inhibitors of
Hepatitis C Virus Comprising Alkyl and Aryl Alanine P2 Moieties. S.
Venkatraman, K. X. Chen, A. Arrasappan, F. G. Njoroge, V. M.
Girijavallabhan, A. K. Ganguly, T. Y. Chan, B. A. McKittrick, N. H. Yao,
A. J. Prongay, and V. S. Madison (filed 4/17/2001, issued as US 6,914,122
B2 on 7/5/2005).
8. Recommendation of SCH503034 (Boceprevir) for Development. HCV Protease
Project Team.
(Recommendation Submitted in 2001). This resulted in the drug Victrelis.
9. Recommendation of SCH900512 (Narlaprevir) for Development. HCV Protease
Project Team
Publications
1. 2012: Venkatraman, S.; Prongay, A.J., and Njoroge, F.G. Discovery of
Boceprevir and Narlaprevir. A case study for role of structure based drug
design. (submitted to J. Med. Chem. as an Invited Review article for ABDD
III).
2. 2010: Tong X; Arasappan A; Bennett F; Chase R; Feld B; Guo Z; Hart A;
Madison V; Malcolm B; Pichardo J; Prongay A; Ralston R; Skelton A; Xia E;
Zhang R; Njoroge F G. Preclinical characterization of the antiviral
activity of SCH 900518 (Narlaprevir), a novel mechanism-based inhibitor
of hepatitis C virus NS3 protease. Antimicrobial agents and
chemotherapy 2010;54(6):2365-70.
3. 2010: Bennett F.; Huang Y.; Hendrata S.; Lovey R.; Bogen S. L; Pan W.;
Guo Z.; Prongay A.; Chen K. X; Arasappan A.; Venkatraman S.; Velazquez
F.; Nair L.; Sannigrahi M.; Tong X.; Pichardo J.; Cheng K.-C.;
Girijavallabhan V.M; Saksena A.K; Njoroge F.G. The introduction of P4
substituted 1-methylcyclohexyl groups into Boceprevir: a change in
direction in the search for a second generation HCV NS3 protease
inhibitor. Bioorganic & medicinal chemistry letters 2010;20(8):2617-21.
4. 2010: Nair L.G; Sannigrahi M.; Bogen S.; Pinto P.; Chen K.X; Prongay A.;
Tong X.; Cheng K-C; Girijavallabhan V.; Njoroge F.G. P4 capped amides and
lactams as HCV NS3 protease inhibitors with improved potency and DMPK
profile. Bioorganic & medicinal chemistry letters 2010;20(2):567-70.
5. 2009: Sheth P.R; Basso A.; Duca J.S; Lesburg C.A; Ogas P.; Gray K.; Nale
L.; Mannarino A.F; Prongay A.J; Le H.V. Thermodynamics of nucleotide and
inhibitor binding to wild-type and ispinesib-resistant forms of human
kinesin spindle protein. Biochemistry 2009;48(46):11045-55.
6. 2009: Venkatraman S.; Blackman M.; Wu W.; Nair L.; Arasappan A.; Padilla
A.; Bogen S.; Bennett F.; Chen K.; Pichardo J.; Tong X.; Prongay A.;
Cheng K.-C.; Girijavallabhan V.; Njoroge FG
Discovery of novel P3 sulfonamide-capped inhibitors of HCV NS3 protease.
Inhibitors with improved cellular potencies. Bioorganic & medicinal
chemistry 2009;17(13):4486-95.
7. 2009: Chen K.X; Nair L.; Vibulbhan B.; Yang W.; Arasappan A.; Bogen S.L;
Venkatraman S.; Bennett F.; Pan W.; Blackman M.L; Padilla A.I; Prongay
A.; Cheng K.-C.; Tong X,; Shih N.-Y.; Njoroge F G.
Second-generation highly potent and selective inhibitors of the hepatitis
C virus NS3 serine protease.
Journal of medicinal chemistry 2009;52(5):1370-9.
8. 2009: Venkatraman S.; Velazquez F.; Wu W.; Blackman M.; Chen KX; Bogen
S.; Nair L.; Tong X.; Chase R.; Hart A.; Agrawal S.; Pichardo J.; Prongay
A.; Cheng K.-C.; Girijavallabhan V.; Piwinski J.; Shih NY.; Njoroge F.G.
Discovery and structure-activity relationship of P1-P3 ketoamide derived
macrocyclic inhibitors of hepatitis C virus NS3 protease. Journal of
medicinal chemistry 2009;52(2):336-46.
9. 2009: Venkatraman S.; Wu W.; Prongay A.; Girijavallabhan V.; Njoroge F.G
Potent inhibitors of HCV-NS3 protease derived from boronic acids.
Bioorganic & medicinal chemistry letters 2009;19(1):180-3.
10. 2008: Hou Y.; McGuinness DE; Prongay AJ; Feld B.; Ingravallo P.; Ogert
RA; Lunn CA; Howe J. A
Screening for antiviral inhibitors of the HIV integrase-LEDGF/p75
interaction using the AlphaScreen luminescent proximity assay. Journal of
biomolecular screening: the official journal of the Society for
Biomolecular Screening 2008;13(5):406-14.
11. 2008: Madison V; Prongay AJ; Guo Z; Yao N; Pichardo J; Fischmann T;
Strickland C; Myers J; Weber PC; Beyer BM; Ingram R; Hong Z; Prosise WW;
Ramanathan L; Taremi SS; Yarosh-Tomaine T; Zhang R; Senior M; Yang RS;
Malcolm B; Arasappan A; Bennett F; Bogen SL; Chen K; Jao E; Liu YT; Lovey
RG; Saksena AK; Venkatraman S; Girijavallabhan V; Njoroge FG Key steps
in the structure-based optimization of the hepatitis C virus NS3/4A
protease inhibitor SCH503034. Journal of synchrotron
radiation 2008;15(Pt 3):204-7.
12. 2008: Tong X; Bogen S; Chase R; Girijavallabhan V; Guo Z; Njoroge FG;
Prongay A; Saksena Al; Skelton A; Xia E; Ralston R Characterization of
resistance mutations against HCV ketoamide protease inhibitors.
Antiviral research 2008;77(3):177-85.
13. 2007: Vel zquez F; Venkatraman S; Wu W; Blackman M; Prongay A;
Girijavallabhan V; Shih N-Y; Njoroge FG Application of ring-closing
metathesis for the synthesis of macrocyclic peptidomimetics as inhibitors
of HCV NS3 protease. Organic letters 2007;9(16):3061-4.
14. 2007: Prongay AJ; Guo Z; Yao N; Pichardo J; Fischmann T; Strickland C;
Myers J; Weber PC; Beyer BM; Ingram R; Hong Z; Prosise WW; Ramanathan L;
Taremi SS; Yarosh-Tomaine T; Zhang R; Senior M; Yang R-S; Malcolm B;
Arasappan A; Bennett F; Bogen SL; Chen K; Jao E; Liu Y-T; Lovey RG;
Saksena AK; Venkatraman S; Girijavallabhan V; Njoroge FG; Madison V
Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-
(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S 1,1-
dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-
dimethyl-3-azabicyclo[3.1.0] hexan-2(S)-carboxamide (Sch 503034) II. Key
steps in structure-based optimization. Journal of medicinal
chemistry 2007;50(10):2310-8.
15. 2007: Liu R; Abid K; Pichardo J; Pazienza V; Ingravallo P; Kong R;
Agrawal S; Bogen S; Saksena A; Cheng K-C; Prongay A; Njoroge FG; Baroudy
BM; Negro F In vitro antiviral activity of SCH446211 (SCH6), a novel
inhibitor of the hepatitis C virus NS3 serine protease. The Journal of
antimicrobial chemotherapy 2007;59(1):51-8.
16. 2006: Venkatraman S; Bogen SL; Arasappan A; Bennett F; Chen K; Jao E;
Liu Y-T; Lovey R; Hendrata S; Huang Y; Pan W; Parekh T; Pinto P; Popov V;
Pike R; Ruan S; Santhanam B; Vibulbhan B; Wu W; Yang W; Kong J; Liang X;
Wong J; Liu R; Butkiewicz N; Chase R; Hart A; Agrawal S; Ingravallo P;
Pichardo J; Kong R; Baroudy B; Malcolm B; Guo Z; Prongay A; Madison V;
Broske L; Cui X; Cheng K-C; Hsieh Y; Brisson J-M; Prelusky D; Korfmacher
W; White R; Bogdanowich-Knipp S; Pavlovsky A; Bradley P; Saksena AK;
Ganguly A; Piwinski J; Girijavallabhan V; Njoroge FG Discovery of (1R,5S)-
N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S 1,1-
dimethylethyl) amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-
dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a
selective, potent, orally bioavailable hepatitis C virus NS3 protease
inhibitor: a potential therapeutic agent for the treatment of hepatitis C
infection. Journal of medicinal chemistry 2006;49(20):6074-86.
17. 2006: Arasappan A; Njoroge FG; Chen KX; Venkatraman S; Parekh TN; Gu H;
Pichardo J; Butkiewicz N; Prongay A; Madison V; Girijavallabhan V P2-P4
macrocyclic inhibitors of hepatitis C virus NS3-4A serine protease.
Bioorganic & medicinal chemistry letters 2006;16(15):3960-5.
18. 2006: Bogen SL; Arasappan A; Bennett F; Chen K; Jao E; Liu Y-T; Lovey
RG; Venkatraman S; Pan W; Parekh T; Pike RE; Ruan S; Liu R; Baroudy B;
Agrawal S; Chase R; Ingravallo P; Pichardo J; Prongay A; Brisson J-M;
Hsieh TY; Cheng K-C; Kemp SJ; Levy OE; Lim-Wilby M; Tamura SY; Saksena
AK; Girijavallabhan V; Njoroge FG Discovery of SCH446211 (SCH6): a new
ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA
replication. Journal of medicinal chemistry 2006;49(9):2750-7.
19. 2006: Malcolm BA; Liu R; Lahser F; Agrawal S; Belanger B; Butkiewicz N;
Chase R; Gheyas F; Hart A; Hesk D; Ingravallo P; Jiang C; Kong R; Lu J;
Pichardo J; Prongay A; Skelton A; Tong X; Venkatraman S; Xia E;
Girijavallabhan V; Njoroge F G SCH 503034, a mechanism-based inhibitor
of hepatitis C virus NS3 protease, suppresses polyprotein maturation and
enhances the antiviral activity of alpha interferon in replicon cells.
Antimicrobial agents and chemotherapy 2006;50(3):1013-20.
20. 2006: Venkatraman S; Njoroge FG; Wu W; Girijavallabhan V; Prongay AJ;
Butkiewicz N; Pichardo J
Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-
aza-bicyclo[2.2.1]heptane-3-carboxylic acid. Bioorganic & medicinal
chemistry letters 2006;16(6):1628-32.
21. 2006: Bogen SL; Ruan S; Liu R; Agrawal S; Pichardo J; Prongay A;
Baroudy B; Saksena AK; Girijavallabhan V; Njoroge FG Depeptidization
efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine
protease: effect on HCV replicon activity. Bioorganic & medicinal
chemistry letters 2006; 16(6):1621-7.
22. 2006: Yi MK; Tong X; Skelton A; Chase R; Chen T; Prongay A; Bogen SL;
Saksena AK; Njoroge FG; Veselenak RL; Pyles RB; Bourne N; Malcolm BA;
Lemon SM Mutations conferring resistance to SCH6, a novel hepatitis C
virus NS3/4A protease inhibitor. Reduced RNA replication fitness and
partial rescue by second-site mutations. The Journal of biological
chemistry 2006;281(12):8205-15.
23. 2006: Chen KX; Njoroge FG; Arasappan A; Venkatraman S; Vibulbhan B;
Yang W; Parekh TN; Pichardo J; Prongay A; Cheng K-C; Butkiewicz N; Yao N;
Madison V; Girijavallabhan V Novel potent hepatitis C virus NS3 serine
protease inhibitors derived from proline-based macrocycles. Journal of
medicinal chemistry 2006;49(3):995-1005.
24. 2006: Tong X; Guo Z; Wright-Minogue J; Xia E; Prongay A; Madison V; Qiu
P; Venkatraman S; Velazquez F; Njoroge FG; Malcolm BA Impact of
naturally occurring variants of HCV protease on the binding of different
classes of protease inhibitors. Biochemistry 2006;45(5):1353-61.
25. 2006: Chen KX; Njoroge FG; Pichardo J; Prongay A; Butkiewicz N; Yao N;
Madison V; Girijavallabhan V Potent 7-hydroxy-1,2,3,4-
tetrahydroisoquinoline-3-carboxylic acid-based macrocyclic inhibitors of
hepatitis C virus NS3 protease. Journal of medicinal
chemistry 2006;49(2):567-74.
26. 2005: Chen KX; Njoroge FG; Vibulbhan B; Prongay A; Pichardo J; Madison
V; Buevich A; Chan T-M
Proline-based macrocyclic inhibitors of the hepatitis C virus:
stereoselective synthesis and biological activity. Angewandte Chemie
(International ed. in English) 2005;44(43):7024-8.
27. 2005: Chen KX; Njoroge FG; Pichardo J; Prongay A; Butkiewicz N; Yao N;
Madison V; Girijavallabhan V Design, synthesis, and biological activity
of m-tyrosine-based 16- and 17-membered macrocyclic inhibitors of
hepatitis C virus NS3 serine protease. Journal of medicinal
chemistry 2005;48(20):6229-35.
28. 2005: Bogen S; Saksena A K; Arasappan A; Gu H; Njoroge F G;
Girijavallabhan V; Pichardo J; Butkiewicz N; Prongay A; Madison V
Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1
cyclopropyl alanine combination for improved potency. Bioorganic &
medicinal chemistry letters 2005;15(20):4515-9.
29. 2005: Chen KX; Njoroge FG; Prongay A; Pichardo J; Madison V;
Girijavallabhan V Synthesis and biological activity of macrocyclic
inhibitors of hepatitis C virus (HCV) NS3 protease. Bioorganic &
medicinal chemistry letters 2005;15(20):4475-8.
30. 2005: Arasappan A; Njoroge F G; Chan T-Y; Bennett F; Bogen S L; Chen K;
Gu H; Hong L; Jao E; Liu Y-T; Lovey R G; Parekh T; Pike R E; Pinto P;
Santhanam B; Venkatraman S; Vaccaro H; Wang H; Yang X; Zhu Z; Mckittrick
B; Saksena A K; Girijavallabhan V; Pichardo J; Butkiewicz N; Ingram R;
Malcolm B; Prongay A; Yao N; Marten B; Madison V; Kemp S; Levy O; Lim-
Wilby M; Tamura S; Ganguly A K Hepatitis C virus NS3-4A serine protease
inhibitors: SAR of P'2 moiety with improved potency. Bioorganic &
medicinal chemistry letters 2005;15(19):4180-4.
31. 2005: Venkatraman S; Njoroge FG; Girijavallabhan VM; Madison VS; Yao
NH; Prongay AJ; Butkiewicz N; Pichardo J Design and synthesis of
depeptidized macrocyclic inhibitors of hepatitis C NS3-4A protease using
structure-based drug design. Journal of medicinal
chemistry 2005;48(16):5088-91.
32. 2004: Arasappan A; Njoroge FG; Parekh TN; Yang X; Pichardo J;
Butkiewicz N; Prongay A; Yao N; Girijavallabhan V Novel 2-
oxoimidazolidine-4-carboxylic acid derivatives as hepatitis C virus NS3-
4A serine protease inhibitors: synthesis, activity, and X-ray crystal
structure of an enzyme inhibitor complex. Bioorganic & medicinal
chemistry letters 2004;14(23):5751-5.
33. 2003: Guo Z; Durkin J; Fischmann T; Ingram R; Prongay A; Zhang R;
Madison V
Application of the lambda-dynamics method to evaluate the relative
binding free energies of inhibitors to HCV protease. Journal of medicinal
chemistry 2003;46(25):5360-4.
34. 1999: Fischmann TO; Hruza A; Niu XD; Fossetta JD; Lunn CA; Dolphin E;
Prongay AJ; Reichert P; Lundell DJ; Narula SK; Weber PC Structural
characterization of nitric oxide synthase isoforms reveals striking
active-site conservation. Nature structural biology 1999;6(3):233-42.
35. 1997: McNemar C; Snow ME; Windsor WT; Prongay A; Mui P; Zhang R; Durkin
J; Le HV; Weber PC Thermodynamic and structural analysis of
phosphotyrosine polypeptide binding to Grb2-SH2.
Biochemistry 1997;36(33):10006-14.
36. 1996: Momany C; Kovari LC; Prongay AJ; Keller W; Gitti RK; Lee BM;
Gorbalenya AE; Tong L; McClure J; Ehrlich LS; Summers MF; Carter C;
Rossmann MG Crystal structure of dimeric HIV-1 capsid protein. Nature
structural biology 1996;3(9):763-70.
37. 1992: Prongay AJ; Williams CH Oxidation-reduction properties of
Escherichia coli thioredoxin reductase altered at each active site
cysteine residue. The Journal of biological chemistry 1992; 267(35)
:25181-8.
38. 1990: Prongay AJ; Smith TJ; Rossmann MG; Ehrlich LS; Carter CA; McClure
J Preparation and crystallization of a human immunodeficiency virus p24-
Fab complex. Proceedings of the National Academy of Sciences of the
United States of America 1990;87(24):9980-4.
39. 1990: Prongay AJ; Williams CH Evidence for direct interaction between
cysteine 138 and the flavin in thioredoxin reductase. A study using
flavin analogs. The Journal of biological chemistry 1990; 265(31):18968-
75.
40. 1989: Prongay AJ; Engelke DR; Williams CH Characterization of two
active site mutations of thioredoxin reductase from Escherichia coli.
The Journal of biological chemistry 1989;264(5):2656-64.
41. 1989: Williams CH; Allison N; Russell GC; Prongay AJ; Arscott LD; Datta
S; Sahlman L; Guest JR
Properties of lipoamide dehydrogenase and thioredoxin reductase from
Escherichia coli altered by site-directed mutagenesis. Annals of the New
York Academy of Sciences 1989;573:55-65.
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