Bill Kinney croped
William A Kinney, PhD
(Principal Investigator) 
Ph: 215-630-5433
Email:bill.kinney@bblumberg.org

 

TRAINING

(1984) Ph.D. Ohio State University

Appointment at the Baruch S. Blumberg Institute:  Professor of Medicinal and Natural Product Chemistry; Director, Natural Products Discovery Institute

Other appointments:
Adjunct Professor, Drexel University College of Medicine
President, IteraMed Consulting

RESEARCH OVERVIEW

Research interest: Natural product discovery using traditional and genomic methods.  Lead optimization of candidates for treating hepatitis B virus (HBV) and other filoviruses.
Research staff: Working closely with Profs. Yanming Du, Jason Clement, Michael Goetz, and John Kulp; and other faculty at the Blumberg Institute.

RESEARCH

The Natural Products Discovery Institute (NPDI) collaborates with a number of academic and industrial partners in natural product discovery in areas including pharmaceuticals, agricultural chemicals, flavor enhancers, cosmetics, consumer products, and nutriceuticals. The NPDI’s internal research is focused on screening its large natural product extract collection for molecules that inhibit hepatitis B, other viruses, and liver cancer.

Metagenomics and genome-driven natural product discovery are providing new methods to detect and activate antibiotic gene clusters. The NPDI is in the process of amplifying and sequencing thousands of actinomycete DNA samples to lay out the biosynthetic potential of the collection.   With the data processing tools, we are able to predict with very high confidence the identity of a significant fraction of the NRPS and PKS gene clusters found in this culture collection. Genomes of priority are de novo sequenced and annotated to refine their gene clusters.  Fermentation and molecular biology techniques are then applied to specific microbes to turn on nascent gene clusters and to produce new natural products of commercially and medically important classes.

RESEARCH SUMMARY

Drug discovery and development of drugs for management of hepatitis B virus (HBV) and other diseases of unmet need.

SELECTED PUBLICATIONS:

“Nonpeptide Urotensin-II Receptor Antagonists: A New Ligand Class Based on Piperazino-Phthalimide and Piperazino-Isoindolinone Subunits” E. C. Lawson, D. K. Luci, S. Ghosh, W. A. Kinney, C. H. Reynolds, J. Qi, C. E. Smith, Y. Wang, L. K. Minor, B. J. Haertlein, T. J. Parry, B. P. Damiano, B. E. Maryanoff, J. Med. Chem. 2009, 52, 7432–7445.

“Generation of Novel, Potent Urotensin-II Receptor Antagonists by Alkylation–Cyclization of Isoindolinone C3-Carbanions” D. K. Luci, E. C. Lawson, S. Ghosh, W. A. Kinney, C. E. Smith, J. Qi, Y. Wang, L. K. Minor, B. E. Maryanoff, Tetrahedron Lett. 2009, 50, 4958-4961.

“Thrombogenic Collagen-Mimetic Peptides: Self-Assembly of Triple Helix-Based Fibrils Driven by Hydrophobic Interactions” M. A. Cejas, W. A. Kinney, C. Chen, J. G. Vinter, H. R. Almond, Jr., K. M. Balss, C. A. Maryanoff, U. Schmidt, M. Breslav, A.Mahan, E. Lacy, C. Yang, B. E. Maryanoff,  Proc. Natl. Acad. Sci. USA 2008, 105, 8525-8530.

“Suzuki–Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing Alpha-V Beta-3/Alpha-V Beta-5 Integrin Antagonist.  Enantioselective Synthesis and Stereochemical Studies” W. A. Kinney, C. A. Teleha, A. S. Thompson, M. Newport, R. Hansen, S. Ballentine, S. Ghosh, A. Mahan, G. Grasa, A. Zanotti-Gerosa, J. Dingenen, C. Schubert, Y. Zhou, G. C. Leo, D. F. McComsey, R. J. Santulli, B. E. Maryanoff , J. Org. Chem. 2008, 73, 2302-2310.

“Studies with an Orally Bioavailable Alpha-V Beta-3/Alpha-V Beta-5 Integrin Antagonist in Animal Models of Ocular Vasculopathy: Retinal Neovascularization in Mice and Retinal Vascular Permeability in Diabetic Rats” R. J. Santulli, W. A. Kinney, S. Ghosh, B. L. DeCorte, L. Liu, R. W. A. Tuman, Z. Zhou, N. Huebert, S. E. Bursell, A. C. Clermont, M. B. Grant, L. C. Shaw, S. A. Mousa, R. A. Galemmo, Jr., D. L. Johnson, B. E. Maryanoff, B. P. Damiano, J. Pharmacol. Exp. Ther. 2008, 324, 894-901.

“Nanoparticles That Display Short Collagen-Related Peptides. Potent Stimulation of Human Platelet Aggregation by Triple Helical Motifs” M. A. Cejas, C. Chen, W. A. Kinney, B. E. Maryanoff, Bioconjugate Chem. 2007, 18, 1025-1027.

“Collagen-Related Peptides: Self-Assembly of Short, Single Strands into a Functional Biomaterial of Micrometer Scale” M. A. Cejas, W. A. Kinney, C. Chen, G. C. Leo, B. A. Tounge, J. G. Vinter, P. P. Joshi, and B. E. Maryanoff, J. Am. Chem. Soc. 2007, 129, 2202-2203.

“Structure-Function Analysis of Urotensin II and Its Use in the Construction of a Ligand-Receptor Working Model” W. A. Kinney, H. R. Almond, Jr., J. Qi, C. E. Smith, R. J. Santulli, L. de Garavilla, P. Andrade-Gordon, D. S. Cho, A. M. Everson, M. A. Feinstein, P. A. Leung, B. E. Maryanoff, Angewandte Chemie, Int. Ed. 2002, 41, 2940-2944.

“A Spermine-Coupled Cholesterol Metabolite from the Shark with Potent Appetite Suppressant and Antidiabetic Properties” M. Zasloff, J. I. Williams, Q. Chen, M. Anderson, T. Maeder, K. Holroyd, S. Jones, W. A. Kinney, K. R. Cheshire, Int. J. Obesity 2001, 25, 689-697.

“A Short Formal Synthesis of Squalamine from a Microbial Metabolite” W. A. Kinney, X. Zhang, J. I. Williams, S. Johnston, R. S. Michalak, M. Deshpande, L. Dostal, J. P. N. Rosazza, Org. Lett. 2000, 2 (19), 2921-2922.

“Aminosterols from the Dogfish Shark Squalus acanthias” M. R. Rao, A. E. Shinnar, L. A. Noecker, T. L. Chao, B. Feibush, B. Snyder, I. Sharkansky, A. Sarkahian, X. Zhang, S. R. Jones, W. A. Kinney, M. Zasloff, J. Nat. Products 2000, 63 (5), 631-635.

“Synthesis of Squalamine Utilizing a Readily Accessible Spermidine Equivalent” X. Zhang, M. N. Rao, S. R. Jones, B. Shao, P. Feibush, M. McGuigan, N. Tzodikov, B. Feibush, I. Sharkansky, B. Snyder, L. M. Mallis, A. Sarkahian, S. Wilder, J. E. Turse, W. A. Kinney, H. J. Kjaersgaard, R. S. Michalak, J. Org. Chem. 1998, 63, 8599-8603.

“Squalamine Inhibits Angiogenesis and Solid Tumor Growth in Vivo and Perturbs Embryonic Vasculature”  A. K. Sills, Jr., J. I. Williams, B. M. Tyler, D. S. Epstein, E. P. Sipos, M. P. McLane, S. Pitchford, K. Cheshire, F. H. Gannon, W. A. Kinney, T. L. Chao, J. D. Davis, M. Donowitz, J. Laterra, M. Zasloff, H. Brem, Cancer Research 1998, 58, 2784-2792.

“Design and Synthesis of [2-(8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]-phosphonic Acid (EAA-090), a Potent N-Methyl-D-aspartate Antagonist, via the Use of 3-Cyclobutene-1,2-dione as an Achiral Alpha-Amino Acid Bioisostere”  W. A. Kinney, M. Abou-Gharbia, D. T. Garrison, J. Schmid, D. M. Kowal, D. R. Bramlett, T. L. Miller, R. P. Tasse, M. M. Zaleska, J. A. Moyer, J. Med. Chem. 1998, 41, 236-246.

“A General Approach to Annulated 4-Cyclooctenones by Aliphatic Claisen Rearrangement. Stereospecific Total Synthesis of Precapnelladiene” W. A. Kinney, M. J. Coghlan, L. A. Paquette, J. Am. Chem. Soc. 1985, 107, 7352.