Daniel J. Sprague
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View article: The Molecular Drug Target of Praziquantel
The Molecular Drug Target of Praziquantel Open
This chapter describes work that led to the identification of the target of praziquantel (PZQ) in parasitic flatworms. The molecular target of this drug is an ion channel of the transient receptor potential family, named TRPM PZQ . TRPM PZ…
View article: BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling
BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling Open
Recognition of methylarginine marks by effector proteins (“readers”) is a critical link between arginine methylation and various cellular processes. Recently, we identified methylation of AKT1 at arginine-391 (R391), but the reader for thi…
View article: A novel HLA Class II presentation prediction algorithm deciphers immunogenic CD4 epitopes specific to KRAS G12C
A novel HLA Class II presentation prediction algorithm deciphers immunogenic CD4 epitopes specific to KRAS G12C Open
Accurate prediction of peptide presentation by HLA molecules is important for generation of effective individualized cancer vaccines and immunotherapies. While presentation prediction algorithms for HLA class I have been successfully appli…
View article: The TRIM33 Bromodomain Recognizes Histone Lysine Lactylation
The TRIM33 Bromodomain Recognizes Histone Lysine Lactylation Open
Histone lysine lactylation (Kla) regulates inflammatory gene expression in activated macrophages and mediates the polarization of inflammatory (M1) to reparative (M2) macrophages. However, the molecular mechanisms and key protein players i…
View article: Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types
Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types Open
Inhibition of BET bromodomains is a novel potential strategy to prevent and treat diabetes mellitus. However, BET inhibitors have negative side effects. We synthesized a BET inhibitor expected to exploit the high zinc concentration in β ce…
View article: TRP drop, TRP drop: a steady patter of anti-schistosomal target illumination
TRP drop, TRP drop: a steady patter of anti-schistosomal target illumination Open
Infections caused by parasitic flatworms impart a significant disease burden. This is well exemplified by the neglected tropical disease schistosomiasis, which afflicts millions of people worldwide. The anti-schistosomal activity of variou…
View article: The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure–Activity Relationships at TRPM<sub>PZQ</sub> Orthologs
The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure–Activity Relationships at TRPM<sub>PZQ</sub> Orthologs Open
The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a …
View article: Target-based discovery of a broad spectrum flukicide
Target-based discovery of a broad spectrum flukicide Open
Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases – for example, the parasitic blood fluke infection, schistosomiasis – are treated with the drug praziquantel (PZQ). However, P…
View article: Molecular and cellular basis of praziquantel action in the cardiovascular system
Molecular and cellular basis of praziquantel action in the cardiovascular system Open
The anthelmintic drug praziquantel (PZQ) causes contraction of parasitic schistosomes as well as constriction of blood vessels within the mesenteric vasculature of the host where the adult blood flukes reside. The contractile action of PZQ…
View article: Natural variation in the binding pocket of a parasitic flatworm TRPM channel resolves the basis for praziquantel sensitivity
Natural variation in the binding pocket of a parasitic flatworm TRPM channel resolves the basis for praziquantel sensitivity Open
The drug praziquantel (PZQ) is the key clinical therapy for treating schistosomiasis and other infections caused by parasitic flatworms. A schistosome target for PZQ was recently identified— a transient receptor potential ion channel in th…
View article: Trisubstituted 1,3,5-Triazines: The First Ligands of the sY12-Binding Pocket on Chemokine CXCL12
Trisubstituted 1,3,5-Triazines: The First Ligands of the sY12-Binding Pocket on Chemokine CXCL12 Open
CXCL12, a CXC-type chemokine, binds its receptor CXCR4, and the resulting signaling cascade is essential during development and subsequently in immune function. Pathologically, the CXCL12-CXCR4 signaling axis is involved in many cancers an…
View article: Substituted Imidazoline Synthesis: A Diastereo- and Enantioselective aza-Henry Route to a Human Proteasome Modulator
Substituted Imidazoline Synthesis: A Diastereo- and Enantioselective aza-Henry Route to a Human Proteasome Modulator Open
The first enantio- and diastereoselective synthesis of Tepe's human proteasome modulator is described. Routes to this and other highly substituted chiral imidazolines generally produce racemic material. Key to the route disclosed here is a…
View article: Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites
Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites Open
BRD4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding s…
View article: Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites
Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites Open
Brd4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding s…
View article: Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites
Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites Open
Brd4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding s…
View article: Nonlinear sequence similarity between the <i>Xist</i> and <i>Rsx</i> long noncoding RNAs suggests shared functions of tandem repeat domains
Nonlinear sequence similarity between the <i>Xist</i> and <i>Rsx</i> long noncoding RNAs suggests shared functions of tandem repeat domains Open
The marsupial inactive X chromosome expresses a long noncoding RNA (lncRNA) called Rsx that has been proposed to be the functional analog of eutherian Xist . Despite the possibility that Xist and Rsx encode related functions, the two lncRN…
View article: Non-linear sequence similarity between the <i>Xist</i> and <i>Rsx</i> long noncoding RNAs suggests shared functions of tandem repeat domains
Non-linear sequence similarity between the <i>Xist</i> and <i>Rsx</i> long noncoding RNAs suggests shared functions of tandem repeat domains Open
The marsupial inactive X chromosome expresses a long noncoding RNA (lncRNA) called Rsx that has been proposed to be the functional analogue of eutherian Xist . Despite the possibility that Xist and Rsx encode related functions, the two lnc…
View article: Diastereo- and enantioselective additions of α-nitro esters to imines for <i>anti</i>-α,β-diamino acid synthesis with α-alkyl-substitution
Diastereo- and enantioselective additions of α-nitro esters to imines for <i>anti</i>-α,β-diamino acid synthesis with α-alkyl-substitution Open
The discovery that a C2-symmetric bis(AMidine) [BAM] catalyst promotes an anti-selective addition of α-substituted α-nitro esters to imines is described, providing α-substituted α,β-diamino ester products with high diastereo- and enantiose…