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Special series: Molecular chaperones in protein folding and disease

Jason E. Gestwicki, Jason E. Gestwicki
2010 Biopolymers  
JASON E. GESTWICKI Department of Pathology and the Life Sciences Institute University of Michigan 210 Washtenaw Ave Ann Arbor, MI 48109-2216  ... 
doi:10.1002/bip.21290 pmid:20039372 fatcat:fakmmaj6oza7lbmej5k2poxrgm

Rehabilitating Mutant GCase

Jennifer N. Rauch, Jason E. Gestwicki
2014 Chemistry and Biology  
In neurodegenerative disorders, insufficient quality control seems to allow accumulation of misfolded proteins (Gestwicki and Garza, 2012) , while in cancer, the aberrant decision to retain oncogenes  ... 
doi:10.1016/j.chembiol.2014.07.010 pmid:25126987 fatcat:oh4rjf5m2nesflc7jazr3bkram

Enantioselective Organocatalytic Hantzsch Synthesis of Polyhydroquinolines

Christopher G. Evans, Jason E. Gestwicki
2009 Organic Letters  
The four-component Hantzsch reaction provides access to pharmaceutically important dihydropyridines. To expand the utility of this method, we have developed a route under organocatalytic conditions with good yields and excellent ee's. Through catalyst screening, we found that a BINOL-phosphoric acid allowed enantioselective synthesis of six-membered heterocycles with a variety of substitution patterns. Multicomponent reactions, such as the Biginelli, 1 Passerini, 2 Ugi, 3 and Hantzsch, provide
more » ... wide variety of important heterocycles. 4 For example, the Hantzsch reaction provides dihydropyridines with activity against calcium channels, multidrug resistance (MDR) proteins, 5-hydroxytryptamine (5-HT) receptors, and anti-inflammatory targets. 5 Beyond their pharmaceutical applications, Hantzsch-derived dihydropyridines are also useful as synthetic tools for reducing imines to amines. 6
doi:10.1021/ol901114f pmid:19527003 pmcid:PMC2727599 fatcat:kdimaz7y3vbjjfqgl4r42rdjla

Inter-receptor communication through arrays of bacterial chemoreceptors

Jason E. Gestwicki, Laura L. Kiessling
2002 Nature  
We also thank E. Yacubova and J. Neffenger for technical help and manuscript preparation.  ...  Adler for supplying E. coli strains AW405, AW550, AW518 and AW701, and for advice. We thank J. S. Parkinson for E. coli strains RP1078, RP5854 and RP2361, and for anti-MCP antibodies.  ...  Multivalent ligand 3 had no effect on the responses to serine in a ggbp (E. coli AW550) or trg (E. coli AW701) mutant (see Supplementary Information) .  ... 
doi:10.1038/415081a pmid:11780121 fatcat:6tasfdx4d5ca7lreysfnovbyya

Tuning chemotactic responses with synthetic multivalent ligands

Jason E Gestwicki, Laura E Strong, Laura L Kiessling
2000 Chemistry and Biology  
We are grateful to E. Lake and J. Adler for helpful suggestions, bacterial strains AW405, AW543, AW550 and AW701, and access to equipment. We also thank G.  ...  Research Paper Tuning chemotactic responses Gestwicki et al. 587 Chemistry & Biology 2000, Vol 7 No 8  ...  E. coli AW405 (a) or RP1078 (cheW, (b)) were pretreated with buffer alone, and E. coli RP1078 were pretreated with compounds 1 (c), 3 (d) or 4 (e) at 5 mM.  ... 
doi:10.1016/s1074-5521(00)00002-8 pmid:11048949 fatcat:gbahfzopzrejbnk473duyknnpa

Synthetische multivalente Liganden als Sonden für die Signaltransduktion

Laura L. Kiessling, Jason E. Gestwicki, Laura E. Strong
2006 Angewandte Chemie  
E) Wenn Corezeptoren als negative Regulatoren wirken, kann die Bindung von Liganden einen Rezeptor aktivieren, indem sie die Abspaltung dieser Corezeptoren herbeiführt.  ...  Ihre Struktur wird geprägt durch die beteiligte APC, durch die Art Laura E. Strong ist stellvertretende Leiterin der Produktentwicklung bei Quintessence Biosciences, Inc.  ... 
doi:10.1002/ange.200502794 fatcat:cnwnkbm4cjfoxfs5l7jx6qs5wu

Target Identification for a Promising Anti-Lupus Drug

Jason E. Gestwicki
2005 Chemistry and Biology  
Treatment Jason E. Gestwicki Department of Pathology of cells with the OSCP ligand, oligomycin, causes a severe drop in intracellular ATP levels and necrosis.  ... 
doi:10.1016/j.chembiol.2005.04.005 pmid:15850977 fatcat:vh5kzrezprhaha4ndnhpsxihcu

Small molecule-directed protein mislocalization

Prasanthi Geda, Nike Bharucha, Craig J. Dobry, Jason E. Gestwicki, Anuj Kumar
2006 Developmental Biology  
Dobry, Jason E.  ...  Gestwicki, Anuj Kumar University of Michigan, Ann Arbor, MI, USA doi:10.1016/j.ydbio.2006.04.300 274 A tale of two morphogen gradients: Identifying Gli targets of Hedgehog Signaling Steven A.  ... 
doi:10.1016/j.ydbio.2006.04.302 fatcat:hr7nvqt5anbfvbpmukhmgd2sve

Inhibitors and chemical probes for molecular chaperone networks

Jason E. Gestwicki, Hao Shao
2018 Journal of Biological Chemistry  
Jason E. Gestwicki and Hao Shao Inhibitors and chemical probes for molecular chaperone networks  ... 
doi:10.1074/jbc.tm118.002813 pmid:30213856 pmcid:PMC6369302 fatcat:y6bwwvocdzedjomdbvpia7wovm

Cell Aggregation by Scaffolded Receptor Clusters

Jason E Gestwicki, Laura E Strong, Christopher W Cairo, Frederick J Boehm, Laura L Kiessling
2002 Chemistry and Biology  
., Gyimesi, E., from a treated sample. Aggregate formation results in fewer particles Wozencraft, C.P., Goldberg, J.B., Sutherland, W.M., Taylor, and a larger MAI value.  ... 
doi:10.1016/s1074-5521(02)00102-3 pmid:11880031 fatcat:5bsdfcnj6vgrraqe24aqwdwonu

Synthetic Multivalent Ligands as Probes of Signal Transduction

Laura L. Kiessling, Jason E. Gestwicki, Laura E. Strong
2006 Angewandte Chemie International Edition  
E) Ligand binding can lead to activation of receptors by separation when co-receptors act as negative regulators.  ...  This tuning is achieved by changes in the phosphorylation of intracellular protein domains and recep-Laura E. Strong is the Vice President of Product Development at Quintessence Biosciences, Inc.  ... 
doi:10.1002/anie.200502794 pmid:16557636 pmcid:PMC2842921 fatcat:wzt42goao5faxnwsklulxnlte4

The remarkable multivalency of the Hsp70 chaperones

Erik R. P. Zuiderweg, Lawrence E. Hightower, Jason E. Gestwicki
2017 Cell stress & chaperones (Print)  
Left column: DnaK count, right column: human HSPA8 count e 3A proximities between compound and E. coli DnaK in the crystal structure (4R5G).  ...  E. coli DnaK (1-388) Left DnaK count, Right: HSPA8 count discovered before by F216 F217 Q260 R261 E217 E218 L262 L263 E267 E268 a E.  ... 
doi:10.1007/s12192-017-0776-y pmid:28220454 pmcid:PMC5352603 fatcat:4rafk3e2bvhjlfe633kbidmofa

Chemical Biology: Learning through Case Studies. By Herbert Waldmann and Petra Janning

Jason E. Gestwicki
2009 ChemBioChem  
Jason E. Gestwicki University of Michigan-Ann Arbor (USA) DOI: 10.1002/cbic.200900458 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ChemBioChem 2009, 10, 2539 -2541  ... 
doi:10.1002/cbic.200900458 fatcat:44kip7swjbbp3h6u6quhjj3efi

Interplay between protein homeostasis networks in protein aggregation and proteotoxicity

Peter M. Douglas, Douglas M. Cyr, Jason E. Gestwicki
2010 Biopolymers  
The misfolding and aggregation of disease proteins is characteristic of numerous neurodegenerative diseases. Particular neuronal populations are more vulnerable to proteotoxicity while others are more apt to tolerate the misfolding and aggregation of disease proteins. Thus, the cellular environment must play a significant role in determining whether disease proteins are converted into toxic or benign forms. The endomembrane network of eukaryotes divides the cell into different subcellular
more » ... tments that possess distinct sets of molecular chaperones and protein interaction networks. Chaperones act as agonists and antagonists of disease protein aggregation to prevent the accumulation of toxic intermediates in the aggregation pathway. Interacting partners can also modulate the conformation and localization of disease proteins and thereby influence proteotoxicity. Thus, interplay between these protein homeostasis network components can modulate the self-association of disease proteins and determine whether they elicit a toxic or benign outcome.
doi:10.1002/bip.21304 pmid:19768782 pmcid:PMC2974844 fatcat:xorxj5txyjh5lfvouojs2giiba

Fine-Tuning Multiprotein Complexes Using Small Molecules

Andrea D. Thompson, Amanda Dugan, Jason E. Gestwicki, Anna K. Mapp
2012 ACS Chemical Biology  
Gestwicki acknowledges the support of NIH R01NS059690 and A. Mapp of NIH RO1CA140667 and GM 2RO106553.  ... 
doi:10.1021/cb300255p pmid:22725693 pmcid:PMC3517816 fatcat:hukph7lu4beozjxhdqsmsckzcm
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