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Drug design, Synthesis and Biological Evaluation

  1. Matthew D. Marsden; Xiaomeng Wu; Sara Mottahedan; Brian Loy; Adam J. Schrier; Brian A. DeChristopher; Akira J. Shimizu; Clayton T. Hardman; Stephen Ho; Christina M. Ramirez; Paul A. Wender; Jerome A. Zack; “Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents”. Virology, 2018, 520, 83-93.

  2. Hao Yang, Daryl Staveness, Steven M. Ryckbosch, Alison D. Axtman, Brian A. Loy, Alexander B. Barnes, Vijay S. Pande, Jacob Schaefer, Paul A. Wender, Lynette Cegelski, “REDOR NMR Reveals Multiple Conformers for a Protein Kinase C Ligand in a Membrane Environment”. ACS Central Science, 2018, 4(1), 89-96.

  3. Paul A. Wender, Clayton T. Hardman, Stephen Ho, Matthew S. Jeffreys, Ryan V. Quiroz, Steven M. Ryckbosch, Akira J. Shimizu, Jack L. Sloane, Matthew C. Stevens, Jana K. Maclaren, "Scalable synthesis of bryostatin 1 and analogs, adjuvant leads against latent HIV", Science, 2017, 358, 218-223.

  4. Liu, Bowen; Ramsundar, Bharath; Kawthekar, Prasad; Shi, Jade; Gomes, Joseph; Luu-Nguyen, Quang; Ho, Stephen; Sloane, Jack; Wender, Paul; Pande, Vijay, "Retrosynthetic reaction prediction using neural sequence-to-sequence models", ACS Central Science, 2017, 358, 218-223.

  5. Brice Albert, Austin Niu, Rashmi Ramani, Robert M. Williams, Garland R. Marshall, Paul A. Wender, Lee Ratner, Alexander B. Barnes, George B. Kyei, "Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analoges display remarkable potency to activate latent HIV without global T-cell activation", Scientific Reports - Nature, August 7, 2017, 7:7456.

  6. Matthew D. Marsden, Brian A. Loy, Xiaomeng Wu, Christina M. Ramirez, Adam J. Schrier, Danielle Murray, Akira Shimizu, Steven M. Ryckbosch, Katherine E. Near, Tae-Wook Chun, Paul A. Wender, Jerome A. Zack, "In vivo activation of latent HIV with a synthetic bryostatin analog effects both latent cell "kick" and "kill" in strategy for virus eradication", PLoS Pathogens, September 21, 2017.

  7. Nancy L. Benner, Xiaoyu Zang, Daniel C. Buehler, Valerie A. Kickhoefer, Michael E. Rome, Leonard H. Rome, Paul A. Wender, "Vault Nanoparticles: Chemical Modifications for Imaging and Enhanced Delivery", ACS Nano., 2017,11(1), 872-881.

  8. Tapan K. Khan, Paul A. Wender, Daniel L. Alkon; "Bryostatin and its synthetic analog rescue dermal fibroblasts from stress and contribute to survival and rejuvenation of human skin equivalents"; J. Cellular Physiology, 2017.

  9. Colin J. McKinlay, Jessica R. Vargas, Timothy R. Blake, Jonathan W. Hardy, Masamitsu Kanada, Christopher H. Contag, Paul A. Wender, and Robert M. Waymouth, "Charge-altering releasable transporters (CARTS) for the delivery and release of messenger RNA in living animals", Proc. Natl. Acad. Sci.., 2017,114(4), E448-E456.

  10. McKinlay, Colin, Waymouth, Robert, Wender, Paul A., "Cell Penetrating, Guanidinium-Rich Oligophosphoesters: Effective and Versatile Molecular Transporters for Drug and Probe Delivery", J.Am.Chem.Soc.., 2016,138(10), 3510-3517.

  11. Steven M. Ryckbosch, Paul A. Wender, Vijay S. Pande, "Molecular Dynamics Simulations Reveal Ligand-controlled Positioning of a Peripheral Protein Complex in Membranes", Nature Comm.., 2017,8, 6.

  12. Rana Abdelnabi, Daryl Staveness, Katherine E. Near, Paul A. Wender, Leen Delang, Johan Neyts, Pieter Leyssen; "Comparative analysis of the anti-chikungunya virus activity of novel bryostatin analogs confirms the existence of a PKC-independent mechanism", Biochemical Pharmacology, 2016, 120, 15-21.

  13. Staveness, D.; Abdelnabi. R.; Schrier, A.J.; Loy, B.A.; Verma, V.A.; DeChristopher, B.A.; Near, K.E.; Neyts. J.; Delang, L.; Leyssen, .; Wender, P.A.; "Simplified Bryostatin Analogs Protect Cells from Chikungyunya Virus-Induced Cell Death", J.Nat.Prod., 2016, 79(4), 675-679. 

  14. Staveness, D.; Abdelnabi. R.; Near, K.E.; Nakagawa, Y.; Neyts, J.; Delang, L.; Leyseen, P.; Wender, P.A., "Inhibition of Chikungunya Virus-Induced Cell Death by Salicylate-Derived Brostatin Analogs Provide Additional Evidence for a PKC-Independent Pathway", J.Nat.Prod., 2016, 79(4), 680-684.

  15. Wender, Paul; Quiroz, Ryan; Stevens, Matthew; "Function Through Synthesis-Informed Design", Acc. Chem. Res.; 2015, 48(3), 752-760.

  16. Loy Brian A., Lesser Adam B., Staveness Daryl, Billingsley Kelvin L., Cegelski Lynette, Wender Paul A., "Toward a biorelevant structure of protein kinase C bound modulators: design, synthesis, and evaluation of labeled bryostatin analogues for analysis with rotational echo double resonance NMR spectroscopy", J Am Chem Soc., 2015, 137(10), 3678-3685. 

  17. Paul A. Wender and Daryl Staveness; "Improved Protein Kinase C Affinity through Final Step Diversification of Simplified Salicylate-Derived Bryostatin Analog Scaffold", Organic Letters, 2014, 16(19), 5140-5143.

  18. Wender, Paul; Nakagawa, Yu; Near, Katherine; Staveness, Daryl; "Computer-Guided Design, Synthesis, and Protein Kinase C Affinity of a New Salicylate-Based Class of Bryostatin Analogs", Organic Letters, 2014, 16(19), 5136-5139.

  19. Wender, P.A.; Axtman, A.D.; Golden, J..; Kee, J.-M.; Sirois, L.E.; Quiroz, R.V.; Stevens, M.C.; "Function through Bio-Inspired, Synthesis-Informed Design: Step-Economical Synthesis of Designed Kinase Inhibitors", Organic Chemistry Frontiers, 2014, 1, 1166-1171.

  20. Wender, P.A., “Toward the Ideal Synthesis and Molecular Function through Synthesis-informed Design; Natural Products Reports, 2014, 31, 433-440.

  21. Wender, P.A.; Donnelly, A.C.; Loy, B.A.; Near, K.E.; Staveness, D., “Rethinking the Role of Natural Products: Function-Oriented Synthesis, Bryostatin and Bryologs;Natural Products in Medicinal Chemistry (Ed: S. Hanessian) Wiley-VCH, 2014, Ch. 14, 475-544.

  22. Elizabeth J. Beans, Dennis Fournogerakis, Carolyn Gauntlett, Lars V. Heumann, Rainer Kramer, Matthew D. Marsden, Tae-Wook Chun, Jerome A. Zack, and Paul A. Wender; "Highly Potent, Synthetically Accessible Prostratin Analos Induce Latent HIV Expression in vitro and ex vivo", Proc. Natl. Acad. Sci., USA, 2013, 110(29), 11698-11703.

  23. Brian A. DeChristopher, Brian A. Loy, Matthew D. Marsden, Adam J. Schrier, Jerome A. Zack, & Paul A. Wender, “Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro”, Nature Chemistry, 2012, 4, 705-710.

  24. DeChristopher, Brian A., Fan, A.C., Felsher, D.W., Wender, Paul A., “”Picolog,” a Synthetically-Available Bryostatin Analog, Inhibits Growth of MYC-Induced Lymphoma in Vivo”; Oncotarget, 2012, 3(1), 58-66.

  25. Lopez-Campistrous, Ana; Song, Xiaohua; Schrier, Adam J.; Wender, Paul, A.; Dower, Nancy A.; Stone, James C.; "Bryostatin Analogue-Induced Apoptosis in Mantle Cell Lymphoma Cell Lines";Experimental Hematology, 2012, 40(8), 646-656.e2.

  26. Wender, P. A.; Baryza, J. L.; Brenner, S. E.; DeChristopher, B. A.; Loy, B. A.; Schrier, A. J.; Verma, V. A. "Function-Oriented Synthesis: Design, Synthesis and Evaluation of Potent Bryostatin Analogs that Modulate PKC Translocation Selectivity." Proc. Natl. Acad. Sci. USA. 2011, 108, 6721-6726.

  27. Wender, P. A.; Loy, B. A.; Schrier, A. J. "Translating Nature's Library: the Bryostatins and Function-Oriented Synthesis." Isr. J. Chem. 2011, 51, 453-472.

  28. Wender, Paul A.; Longcore, Kate E.; “Apoptolidins E and F, New Glycosyated Macrolactones Isolated from Nocardopsis sp.” Organic Letters, 2009, 5474-5477.

  29. Wender, Paul A.; Miller, Benjamin L.; "Synthesis at the Molecular Frontier", Nature, 2009, 460, 197-201.

  30. Lewis, Chad A.; Longcore, Kate E.; Miller, Scott J.; Wender, Paul A. “An Approach to the Site-Selective Diversification of Apoptolidin A with Peptide-Based Catalysts”, Journal of Natural Products, 2009, 72(10), 1864-1869.

  31. Mooberry, Susan; Hilinski, Michael; Clark, Erin; and Wender, Paul “Function-Oriented Synthesis: Biological Evaluation of Laulimalide Analogues Derived from a Last Step Cross Metathesis Diversification Strategy” Molecular Pharmaceutics; 2008; 5, 829-838.

  32. Wender, P.A.; DeChristopher, B.A.; Schrier, A.J. "Efficient Synthetic Access to a New Family of Highly Potent Bryostatin Analogues via a Prins-Drive Macrocyclization Strategy", J. Am. Chem. Soc.; 2008; 130(21); 6658-6659.

  33. Wender, P. A.; Verma, V. A. “The Design, Synthesis, and Evaluation of C7 Diversified Bryostatin Analogs Reveals a Hot Spot for PKC Affinity,”Org. Lett. 2008, 10, 3331.

  34. Wender, Paul A.; Verma, Vishal A.; Paxton, Thomas J.; Pillow, Thomas H. "Function Oriented Synthesis, Step Economy, and Drug Design", Accts. Chem. Res. 2008, 40-49. Abstract, PDF.

  35. Wender, P. A.; Longcore, K. E. "Isolation, Structure Determination, and Anti-Cancer Activity of Apoptolidin D" Org. Lett. 2007, 9, 691-694.

  36. Wender, P. A.; Baryza, J. L.; Hilinski, M. K.; Horan, J. C.; Kan, C.; Verma, V. A., "Beyond Natural Products: Synthetic Analogues of Bryostatin", In Drug Discovery Research: New Frontiers in the Post-Genomic Era; Huang, Z.; Ed.; Wiley-VCH: 2007, 127-162.

  37. Wender, P. A.; Horan, J. C.; Verma, Vishal A. "Total Synthesis and Initial Biological Evaluation of New B-Ring-Modified Bryostatin Analogues"Org. Lett. 2006, 8, 5299-5302.

  38. Wender, P. A.; Horan, J. C. "Synthesis and PKC Binding of a New Class of A-Ring Diversifiable Bryostatin Analogues Utilizing a Double Asymmetric Hydrogenation and Cross-Coupling Strategy" Org. Lett. 2006, 8, 4581-4584.

  39. Wender, P. A.; Hilinski, M. K.; Skaanderup, P. R.; Soldermann, N. G.; Mooberry, S. L. "Pharmacophore mapping in the laulimalide series: total synthesis of a vinylogue for a late-stage metathesis diversification strategy" Org. Lett. 2006, 8, 4105-4108.

  40. Clark, E. A.; Hills, P. M.; Davidson, B. S.; Wender, P. A.; Mooberry, S. L. "Laulimalide and synthetic laulimalide analogues are synergisitic with paclitaxel and 2-methoxyestradiol" Molecluar Pharmaceutics 2006, 3, 457-467.

  41. Wender, P. A.; Verma, V. A. "Design, Synthesis, and Biological Evaluation of a Potent, PKC Selective, B-Ring Analog of Bryostatin" Org. Lett.2006, 8, 1893-1896.

  42. Wender, P. A.; Hilinski, M. K.; Soldermann, N.; Mooberry, S. L. "Total Synthesis and Biological Evaluation of 11-Desmethyllaulimalide, a Highly Potent Simplified Laulimalide Analogue" Org. Lett. 2006, 8, 1507-1510.

  43. Wender, P. A.; Jankowski, O. D.; Longcore, K.; Tabet, E. A.; Seto, H.; Tomikawa, T. "Correlation of F0F1-ATPase Inhibition and Antiproliferative Activity of Apoptolidin Analogues" Org. Lett. 2006, 8, 589-592.

  44. Wender, P. A.; Sukopp, M.; Longcore, K. "Apoptolidins B and C: Isolation, Structure Determination, and Biological Activity" Org. Lett. 2005, 7, 3025-3028.

  45. Wender, P. A.; Clarke, M. O.; Horan, J. C. "Role of the A-Ring of Bryostatin Analogues in PKC Binding: Synthesis and Initial Biological Evaluation of New A-Ring-Modified Bryologs" Org. Lett. 2005, 7, 1995-1998.

  46. Wender, P. A.; Baryza, J. L. "Identification of a Tunable Site in Bryostatin Analogs: C20 Bryologs Through Late Stage Diversification" Org. Lett.2005, 7, 1177-1180.

  47. Wender, P. A.; Hilinski, M. K.; Mayweg, A. V. W. "Late-stage Intermolecular C-H Activation for Lead Diversification: A Highly Chemoselective Oxyfunctionalization of the C-9 Position of Potent Bryostatin Analogues" Org. Lett. 2005, 7, 79-82

  48. Wender, P. A.; Baryza, J. L.; Brenner, S. E.; Clarke, M. O.; Craske, M. L.; Horan, J. C.; Meyer, T. "Function Oriented Synthesis: The Design, Synthesis, PKC Binding and Translocation Activity of a New Bryostatin Analog." Curr. Drug Disc. Tech., 2004; 1, 1-11.

  49. Mooberry, S. L.; Randall-Hlubek, D. A.; Leal, R. M.; Hegde, S. G.; Hubbard, R. D.; Zhang, L.; Wender, P. A. "Microtubule-Stabilizing Agents Based on Designed Laulimalide Analogues" Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 8803-8808.

  50. Wender, P. A.; Hegde, S. G.; Hubbard, R. D.; Zhang, L.; Mooberry, S. L. "Synthesis and Biological Evaluation of (-)-Laulimalide Analogues" Org. Lett., 2003, 5, 3507-3509.

  51. Wender, P. A.; Jankowski, O. D.; Tabet, E. A.; Seto, H. "Facile Synthetic Access to and Biological Evaluation of the Macrocyclic Core of Apoptolidin " Org. Lett., 2003, 5, 2299-2302. 

  52. Wender, P. A.; Mayweg, A. V. W.; VanDeusen, C. L. "A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue" Org. Lett., 2003; 5, 277-279.

  53. Wender, P.A.; D'Angelo, N.; "A Facile C-C bond cleavage in epoxides and its use for the synthesis of oxygenated heterocycles by a ring expansion strategy" ChemTracts, 2002; 15, 183-188.

  54. Wender, P. A.; Jankowski, O. D.; Tabet, E. A.; Seto, H. "Toward a Structure-Activity Relationship for Apoptolidin: Selective Functionalization of the Hydroxyl Group Array" Org. Lett., 2003; 5, 487-490.

  55. Wender, P. A.; Baryza, J.; Bennett, C.; Bi, C.; Brenner, S. E.; Clarke, M.; Horan, J.; Kan, C.; Lacote, E.; Lippa, B.; Nell, P.; Turner, T. "The Practical Synthesis of a Novel and Highly Potent Analog of Bryostatin" J. Am. Chem. Soc. 2002, 124, 13648-13649.

  56. Wender, P. A.; Gulledge, A. V.; Jankowski, O. D.; Seto, H. "Isoapoptolidin: Structure and Activity of the Ring-Expanded Isomer of Apoptolidin"Organic Letters, 2002, 4, 3819-3822.

  57. Wender, P. A.; Lippa B. "Synthesis and Biological Evaluation of Bryostatin Analogues: the Role of the A-Ring" Tetrahedon Lett. 2000, 41, 1007-1011.

  58. Wender, P. A.; Hinkle, K. W.; Koehler, M. F. T.; Lippa, B. "The Rational Design of Potential Chemotherapeutic Agents: Synthesis of Bryostatin Analogues" Med. Res. Rev. 1999, 19, 388-407.

  59. Wender, P. A.; Koehler, M. F. T.; Wright, D. L.; Irie, K. "Mapping Phorbol Ester Binding Domains of Protein Kinase C (PKC): the Design, Synthesis and Biological Activity of Novel Phorbol Ester Dimers" Synthesis 1999, 1401-1406.

  60. Wender, P. A.; Debrabander, J; Harran P. G.; Jimenez J. M.; Koehler M. F. T.; Lippa, B; Park, C. M.; Siedenbiedel, C.; Pettit, G. R. "The Design, Computer Modeling, Solution Structure, and Biological Evaluation of Synthetic Analogs of Bryostatin 1" Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 6624-6629.

  61. Wender, P. A.; Debrabander, J.; Harran, P. G.; Jimenez, J. M.; Koehler, M. F. T.; Lippa, B.; Park, C. M.; Shiozaki, M."Synthesis of the First Members of A New Class of Biologically Active Bryostatin Analogues" J. Am. Chem. Soc. 1998, 120, 4534-4535.

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