Research Topics
| P A WenderSummaryAffiliation: Stanford University Country: USA Publications
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Publications
Synthesis and PKC binding of a new class of a-ring diversifiable bryostatin analogues utilizing a double asymmetric hydrogenation and cross-coupling strategyPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 8:4581-4. 2006..An aryl bromide diversification site is incorporated allowing access to systematically varied analogues. The new analogues all exhibit potent, nanomolar affinity to PKC...- An efficient, scalable synthesis of the molecular transporter octaarginine via a segment doubling strategyP A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 3:3229-32. 2001.... - A new class of simplified phorbol ester analogues: synthesis and binding to PKC and eta PKC-C1B (eta PKC-CRD2)P A Wender
Department of Chemistry, Stanford University, California 94305, USA
Org Lett 1:1009-12. 1999..The binding of these analogues to protein kinase C (PKC) and the truncated peptide eta PKC-C1B (eta PKC-CRD2) is also reported... - Asymmetric total synthesis of (+)-aphanamol I based on the transition metal catalyzed [5 + 2] cycloaddition of allenes and vinylcyclopropanesP A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 2:2323-6. 2000..The metal-catalyzed [5 + 2] cycloaddition of this precursor proceeds with complete chemo, endo/exo, and diastereoselectivity in 93% yield, representing an effective general route to bicyclo[5.3.0]decane derivatives... 
The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transportersP A Wender
Departments of Chemistry and Neurology, Stanford University, Stanford, CA 94305 5080, USA
Proc Natl Acad Sci U S A 97:13003-8. 2000..Overall, a transporter has been developed that is superior to Tat(49-57), protease resistant, and more readily and economically prepared...- Asymmetric synthesis of the tricyclic core of NGF-inducing cyathane diterpenes via a transition-metal-catalyzed [5 + 2] cycloadditionP A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 3:2105-8. 2001..This strategy provides efficient access (14 steps and 13% overall yield) to potential analogues as well as precursors of nerve growth factor (NGF)-inducing diterpenes... - Molecular transporters for peptides: delivery of a cardioprotective epsilonPKC agonist peptide into cells and intact ischemic heart using a transport system, R(7)L Chen
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA
Chem Biol 8:1123-9. 2001..CONCLUSIONS: Our data suggest that R(7) converts a peptide lead into a potential therapeutic agent for the ischemic heart... - The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1P A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305 5080, USA
Proc Natl Acad Sci U S A 95:6624-9. 1998..8-170 ng/ml) against several human cancer cell lines, providing an important step toward the development of simplified, synthetically accessible analogs of the bryostatins... - Single-molecule motions of oligoarginine transporter conjugates on the plasma membrane of Chinese hamster ovary cellsH L Lee
Department of Chemistry, Stanford University, Stanford, California 94305, USA
J Am Chem Soc 130:9364-70. 2008.... - Pharmacophore mapping in the laulimalide series: total synthesis of a vinylogue for a late-stage metathesis diversification strategyPaul A Wender
Departments of Chemistry and Molecular Pharmacology, Stanford University, Stanford, CA 94305 5080, USA
Org Lett 8:4105-8. 2006..This step-economical strategy enables the rapid synthesis of new analogues using alkenes as an inexpensive, abundantly available diversification feedstock... - Molecular transporters: synthesis of oligoguanidinium transporters and their application to drug delivery and real-time imagingElena A Goun
Stanford University, Department of Chemistry Stanford, CA 94305, USA
Chembiochem 7:1497-515. 2006 - Total synthesis and initial biological evaluation of new B-ring-modified bryostatin analogsPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 8:5299-302. 2006..The resulting new analogs exhibit potent nanomolar or picomolar affinity to protein kinase C (PKC), comparable to or better than that found for bryostatin... - Studies on oxidopyrylium [5+2] cycloadditions: toward a general synthetic route to the C12-hydroxydaphnetoxinsPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 8:5373-6. 2006..Depending on the choice of protecting groups and solvent, the oxidopyrylium-alkene [5+2] cycloaddition originating from A provides cycloadduct diastereomer B or C with good to excellent selectivity... - Laulimalide and synthetic laulimalide analogues are synergistic with paclitaxel and 2-methoxyestradiolErin A Clark
Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, Texas 78227, USA
Mol Pharm 3:457-67. 2006..These important findings suggest that specific combinations of microtubule-targeting agents should be considered for clinical utilities as they have excellent potential to improve clinical response... - Releasable luciferin-transporter conjugates: tools for the real-time analysis of cellular uptake and releaseLisa R Jones
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA
J Am Chem Soc 128:6526-7. 2006..The process provides a method to assay uptake and release of free luciferin as a function of variations in the releasable linker and in the transporter... - Intracellular cargo delivery by an octaarginine transporter adapted to target prostate cancer cells through cell surface protease activationElena A Goun
Department of Chemistry, Stanford University, Stanford, California 94305, USA
Bioconjug Chem 17:787-96. 2006..These APTD peptide-based molecules may facilitate targeted delivery of therapeutics or imaging agents to PSA-expressing prostate cancers... - Asymmetric catalysis of the [5 + 2] cycloaddition reaction of vinylcyclopropanes and pi-systemsPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305, USA
J Am Chem Soc 128:6302-3. 2006..A predictive model for the selectivity is also presented... - RhI-catalyzed C-C bond activation: seven-membered ring synthesis by a [6+1] carbonylative ring-expansion reaction of allenylcyclobutanesPaul A Wender
Department of Chemistry, Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305-5080, USA
Angew Chem Int Ed Engl 45:3957-60. 2006 - Design, synthesis, and biological evaluation of a potent, PKC selective, B-ring analog of bryostatinPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 8:1893-6. 2006..This analog exhibits potent, single-digit nanomolar affinity to PKC and selectively translocates novel PKC isozymes... - Total synthesis and biological evaluation of 11-desmethyllaulimalide, a highly potent simplified laulimalide analoguePaul A Wender
Departments of Chemistry and Molecular Pharmacology, Stanford University, Stanford, California 94305 5080, USA
Org Lett 8:1507-10. 2006..This new lead retains the anticancer function of laulimalide... - Cyclopentadienone synthesis by rhodium(I)-catalyzed [3 + 2] cycloaddition reactions of cyclopropenones and alkynesPaul A Wender
Departments of Chemistry and of Molecular Pharmacology, Stanford University, Stanford, CA 94305 5080, USA
J Am Chem Soc 128:14814-5. 2006..The reaction is readily scalable to produce gram quantities of cycloadduct and provides a unique and versatile route to CPDs that would be otherwise difficult to obtain... - Isolation, structure determination, and anti-cancer activity of apoptolidin DPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 9:691-4. 2007..Its equilibration with isoapoptolidin D and characterization of the latter are also described. [structure: see text]... - Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transportersElena A Dubikovskaya
Department of Chemistry and Chemical and Systems Biology, Stanford University, Stanford, CA 94305 5080, USA
Proc Natl Acad Sci U S A 105:12128-33. 2008.... - The design, synthesis, and evaluation of C7 diversified bryostatin analogs reveals a hot spot for PKC affinityPaul A Wender
Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305 5080, USA
Org Lett 10:3331-4. 2008..Several analogs exhibit single-digit nanomolar affinity to PKC and display superior activity compared to bryostatin against the leukemia cell line K562... - Efficient synthetic access to a new family of highly potent bryostatin analogues via a Prins-driven macrocyclization strategyPaul A Wender
Departments of Chemistry and Chemical and Systems Biology, Stanford University, Stanford, California 94305 5080, USA
J Am Chem Soc 130:6658-9. 2008..These tetrahydropyranyl B-ring analogues are among our most potent and efficacious analogues to date, exhibiting nanomolar and picomolar activities in protein kinase C affinity assays as well as in cellular antiproliferation assays... - Practical synthesis of prostratin, DPP, and their analogs, adjuvant leads against latent HIVPaul A Wender
Department of Chemistry, Stanford University, 337 Campus Drive, Stanford, CA 94305, USA
Science 320:649-52. 2008..This synthesis reliably supplies gram quantities of the therapeutically promising natural products, hitherto available only in low and variable amounts from natural sources, and opens access to a variety of new analogs... - Substituent effects, reactant preorganization, and ligand exchange control the reactivity in Rh(I)-catalyzed (5+2) cycloadditions between vinylcyclopropanes and alkynesPeng Liu
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA
Angew Chem Int Ed Engl 47:3939-41. 2008 - Origins of differences in reactivities of alkenes, alkynes, and allenes in [Rh(CO)2Cl]2-catalyzed (5 + 2) cycloaddition reactions with vinylcyclopropanesZhi-Xiang Yu
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, College of Chemistry, Peking University, Beijing 100871, PR China
J Am Chem Soc 130:2378-9. 2008 - The design of guanidinium-rich transporters and their internalization mechanismsPaul A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305, USA
Adv Drug Deliv Rev 60:452-72. 2008..Some GRT drug conjugates have been advanced into clinical trials. This review will provide an overview of recent work pertinent to the design and mechanism of uptake of GRTs... - Function-oriented synthesis, step economy, and drug designPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Acc Chem Res 41:40-9. 2008..This approach enables the development of synthetically innovative strategies while targeting therapeutically novel structures... - Nickel(0)-catalyzed [2 + 2 + 2 + 2] cycloadditions of terminal diynes for the synthesis of substituted cyclooctatetraenesPaul A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA
J Am Chem Soc 129:13402-3. 2007 - A computationally designed Rh(I)-catalyzed two-component [5+2+1] cycloaddition of ene-vinylcyclopropanes and CO for the synthesis of cyclooctenonesYuanyuan Wang
Beijing National Laboratory for Molecular Sciences (BNLMS, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
J Am Chem Soc 129:10060-1. 2007 - Real-time analysis of uptake and bioactivatable cleavage of luciferin-transporter conjugates in transgenic reporter micePaul A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305 5080, USA
Proc Natl Acad Sci U S A 104:10340-5. 2007.... - Function-oriented synthesis: studies aimed at the synthesis and mode of action of 1alpha-alkyldaphnane analoguesPaul A Wender
Department of Chemistry and Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305 5080, USA
Org Lett 9:1829-32. 2007..A completely diastereoselective palladium-catalyzed enyne cyclization was then employed to establish the A-ring with a C1 appendage... - Metal-catalyzed [2+2+1] cycloadditions of 1,3-dienes, allenes, and COPaul A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA
Angew Chem Int Ed Engl 45:2459-62. 2006 - Function oriented synthesis: the design, synthesis, PKC binding and translocation activity of a new bryostatin analogPaul A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305, USA
Curr Drug Discov Technol 1:1-11. 2004.... - Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analoguesPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 8:589-92. 2006..Potent F(0)F(1)-ATPase inhibition was not a sufficient determinant of antiproliferative activity for several analogues, suggesting the existence of a secondary biological target or more complex mode of action for apoptolidin... - Synthesis and biological evaluation of (-)-laulimalide analoguesPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305, USA
Org Lett 5:3507-9. 2003..Significantly, like laulimalide, these analogues are poor substrates for the drug transport protein P-glycoprotein (Pgp) and are thus effective against Taxol-resistant cell lines... - Arginine-based molecular transporters: the synthesis and chemical evaluation of releasable taxol-transporter conjugatesThorsten A Kirschberg
CellGate, Inc, 552 Del Rey Avenue, Sunnyvale, California 95085, USA
Org Lett 5:3459-62. 2003..The resultant taxol-transporter conjugates are highly water soluble and release free taxol with half-lives of minutes to hours depending on the pH and the linker structure... - Gene transfer via reversible plasmid condensation with cysteine-flanked, internally spaced arginine-rich peptidesZurab Siprashvili
VA Palo Alto Healthcare System, Palo Alto, CA 94305, USA
Hum Gene Ther 14:1225-33. 2003..Thus, cysteine-flanked, internally spaced arginine-rich (CFIS-R) peptides represent a new approach to efficient nonviral plasmid delivery using rationally designed protein transduction domains... - Facile synthetic access to and biological evaluation of the macrocyclic core of apoptolidinPaul A Wender
Department of Chemistry, Stanford University, Stanford, CA 94305 5080, USA
Org Lett 5:2299-302. 2003..The ability of compounds derived from this cleavage to inhibit mitochondrial F(0)F(1)-ATPase is reported. [structure: see text].. - Guanidinium rich peptide transporters and drug deliveryLee R Wright
Department of Chemistry, Stanford University, Stanford, California 95304, USA
Curr Protein Pept Sci 4:105-24. 2003..Lead conjugates in this area are currently in clinical trials... - Isoapoptolidin: structure and activity of the ring-expanded isomer of apoptolidinPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 4:3819-22. 2002..Isoapoptolidin's ability to inhibit mitochondrial F0F1-ATPase is over 10-fold less than that of apoptolidin... - Toward a structure-activity relationship for apoptolidin: selective functionalization of the hydroxyl group arrayPaul A Wender
Department of Chemistry, Stanford University, Stanford, California, 94305 5080, USA
Org Lett 5:487-90. 2003..The syntheses of these derivatives and their ability to inhibit F(0)F(1)-ATPase are reported... - A concise, selective synthesis of the polyketide spacer domain of a potent bryostatin analoguePaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 5:277-9. 2003..The spacer domain 1 is obtained in 10 steps with a 25% overall yield and is readily incorporated into the synthesis of 2... - The practical synthesis of a novel and highly potent analogue of bryostatinPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
J Am Chem Soc 124:13648-9. 2002..Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer... - Oligocarbamate molecular transporters: design, synthesis, and biological evaluation of a new class of transporters for drug deliveryPaul A Wender
Department of Chemistry, Stanford University, California 94305 5080, USA
J Am Chem Soc 124:13382-3. 2002..Significantly, this new family of transporters also enables uptake into the formidable skin barrier of a probe molecule that by itself does not penetrate skin... - Arginine-rich molecular transporters for drug delivery: role of backbone spacing in cellular uptakeJonathan B Rothbard
CellGate Inc, 552 Del Rey Avenue, Sunnyvale, California 94085, USA
J Med Chem 45:3612-8. 2002..This study led to the identification of a new series of highly efficient molecular transporters... - A new synthetic approach to the C ring of known as well as novel bryostatin analoguesPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 5:4549-52. 2003..The convergent approach, illustrated above, requires fewer steps and offers greater flexibility in rapidly accessing diverse C ring analogues... - Microtubule-stabilizing agents based on designed laulimalide analoguesSusan L Mooberry
Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, 7620 Northwest Loop 410, San Antonio, TX 78227, USA
Proc Natl Acad Sci U S A 101:8803-8. 2004..In summary, analogues of laulimalide designed to minimize or eliminate its intrinsic instability have been synthesized, and some have been found to retain the unique biological activities of laulimalide... - Total synthesis of (-)-laulimalidePaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
J Am Chem Soc 124:4956-7. 2002..Laulimalide was synthesized in 25 steps (longest linear; 36 overall) in 3.5% overall yield, providing a uniquely short and efficient route to 1 and its analogues... - Actin is the primary cellular receptor of bistramide AAlexander V Statsuk
Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA
Nat Chem Biol 1:383-8. 2005.... - Dendrimeric molecular transporters: synthesis and evaluation of tunable polyguanidino dendrimers that facilitate cellular uptakePaul A Wender
Department of Chemistry and Department of Molecular Pharmacology, Stanford University, California 94305 5080, USA
Org Lett 7:4815-8. 2005..While the dendrimers varied significantly in their ability to enter a human lymphocyte cell line, the best transporters out-performed an oligoarginine reference standard... - Apoptolidins B and C: isolation, structure determination, and biological activityPaul A Wender
Department of Chemistry, Stanford University, California 94305 5080, USA
Org Lett 7:3025-8. 2005..These new agents are found to have antiproliferative activity on par with or better than apoptolidin itself in an assay with H292 lung cancer cells... - Role of the A-ring of bryostatin analogues in PKC binding: synthesis and initial biological evaluation of new A-ring-modified bryologsPaul A Wender
Department of Chemistry, Stanford University, California 94305 5080, USA
Org Lett 7:1995-8. 2005..All three analogues exhibit potent, single-digit nanomolar affinity to protein kinase C... - Identification of a tunable site in bryostatin analogs: C20 Bryologs through late stage diversificationPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
Org Lett 7:1177-80. 2005..The use of this site in a late-stage diversification strategy has enabled the facile synthesis of a variety of new C20 analogs, all of which retain nanomolar affinity for PKC, in agreement with our pharmacophore hypothesis... - Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cellsJonathan B Rothbard
Department of Chemistry, Stanford University, Stanford CA 94305, USA
Adv Drug Deliv Rev 57:495-504. 2005..This mechanism could also be involved in the translocation of guanidinium-rich molecules that are endocytosed due to their size or the conditions of the assay, across the endosomal membrane... - Late-stage intermolecular CH activation for lead diversification: a highly chemoselective oxyfunctionalization of the C-9 position of potent bryostatin analoguesPaul A Wender
Department of Chemistry, Stanford University, Stanford, California 94305 8050, USA
Org Lett 7:79-82. 2005..Complete selectivity for C-9 hydroxylation was restored upon acylation of the C-26 secondary alcohol... - Effect of serum and antioxidants on the immunogenicity of protein kinase C-activated chronic lymphocytic leukemia cellsCaitlin Hammond
Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women's College Health Sciences Center, 2075 Bayview Avenue, Toronto, Canada M4N 3M5
J Immunother (1997) 28:28-39. 2005..The observation that CLL cells can acquire features of dendritic cells that promote type 1 immunity may find clinical application in immunotherapeutic strategies for this disease... - Synthetic bryostatin analogues activate the RasGRP1 signaling pathwayJames C Stone
Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
J Med Chem 47:6638-44. 2004..In addition to sharing potential anticancer properties with bryostatin 1, compounds 1 and 2 might be clinically useful as modulators of the immune system... - Simplified analogs of bryostatin with anticancer activity display greater potency for translocation of PKCdelta-GFPJeremy L Baryza
Department of Chemistry, Stanford University, Stanford, CA 94305, USA
Chem Biol 11:1261-7. 2004.... - Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cellsJonathan B Rothbard
Department of Chemistry, Stanford University, Stanford, California 94305, USA
J Am Chem Soc 126:9506-7. 2004..The complex dissociates on the inner leaf of the membrane, and the transporter enters the cytosol. This hypothesis does not preclude uptake by other mechanisms, including endocytosis, which is likely to dominate with large cargos... - Photoinduced cleavage of DNA by bromofluoroacetophenone-pyrrolecarboxamide conjugatesPaul A Wender
Department of Chemistry, Stanford University, CA 94305, USA
Bioorg Med Chem Lett 13:1763-6. 2003..The DNA cleaving activities of 2'-bromo-4'-fluoroacetophenone derivatives were larger than those of 4'-bromo-2'-fluoroacetophenone derivatives... - Nanotube molecular transporters: internalization of carbon nanotube-protein conjugates into Mammalian cellsNadine Wong Shi Kam
Department of Chemistry, Stanford University, Stanford, California 94305, USA
J Am Chem Soc 126:6850-1. 2004..The biocompatibility and unique physical, electrical, optical, and mechanical properties of nanotubes provide the basis for new classes of materials for drug, protein, and gene delivery applications...