Charles S. Craik
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View article: 96 Real-time <i>in vivo</i> imaging of therapeutic biodistribution with a miniaturized, implantable fluorescence imager
96 Real-time <i>in vivo</i> imaging of therapeutic biodistribution with a miniaturized, implantable fluorescence imager Open
View article: Antibody Reveals Conformational Latch Controlling Herpesvirus Proteases
Antibody Reveals Conformational Latch Controlling Herpesvirus Proteases Open
Human herpesviruses (HHVs) are widespread pathogens that cause severe disease. Their replication depends on the HHV protease (HHV Pr), an enzyme essential for capsid maturation. Because HHV Pr must dimerize to become catalytically active, …
View article: Identifying protease-activated targets and exploring therapeutic applications
Identifying protease-activated targets and exploring therapeutic applications Open
We believe that identifying substrates activated by disease-associated proteases, enabled by recent technological advances, will lead to deeper biological insights. When combined with peptide-level techniques, these discoveries can drive t…
View article: Structures of Fab-stabilized CHIP reveal a conformational switch important in E3 ligase and chaperone functions
Structures of Fab-stabilized CHIP reveal a conformational switch important in E3 ligase and chaperone functions Open
Carboxyl terminus of Hsc70-interacting protein (CHIP/STUB1) is a U-box E3 ligase essential for protein quality control, targeting misfolded or damaged proteins for clearance and conducting chaperone-like functions by suppressing aggregatio…
View article: Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus M <sup>Pro</sup> inhibitors with potent in vivo efficacy
Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus M <sup>Pro</sup> inhibitors with potent in vivo efficacy Open
The main protease (M Pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a validated drug target. Starting with a lead-like dihydrouracil chemotype identified in a large-library docking campaign, we improved M Pro inhi…
View article: On-Resin Assembly of Macrocyclic Inhibitors of <i>Cryptococcus neoformans</i> May1: A Pathway to Potent Antifungal Agents
On-Resin Assembly of Macrocyclic Inhibitors of <i>Cryptococcus neoformans</i> May1: A Pathway to Potent Antifungal Agents Open
Macrocyclic inhibitors have emerged as a privileged scaffold in medicinal chemistry, offering enhanced selectivity, stability, and pharmacokinetic profiles compared to their linear counterparts. Here, we describe a novel, on-resin macrocyc…
View article: Post-vaccination SARS-CoV-2 neutralizing antibodies in pregnant women receiving biologics for inflammatory bowel disease
Post-vaccination SARS-CoV-2 neutralizing antibodies in pregnant women receiving biologics for inflammatory bowel disease Open
Inflammatory bowel disease (IBD) treatments and pregnancy can independently modulate immune responses, but the combined effects on SARS-CoV-2 vaccine-induced immunity are poorly understood. This study explores the efficacy of SARS-CoV-2 va…
View article: Cryo-EM Determines the Epitope of a 28 kD Viral Protease in Complex with an Antibody Fragment
Cryo-EM Determines the Epitope of a 28 kD Viral Protease in Complex with an Antibody Fragment Open
Cryo-Electron Microscopy (cryo-EM) is an enabling technology for structure-guided antibody drug design. The 50 kD antibody fragment antigen-binding (Fab) is particularly amenable to cryo-EM due to its clear features and its ability to make…
View article: Recombinant antibodies inhibit enzymatic activity of the E3 ubiquitin ligase CHIP via multiple mechanisms
Recombinant antibodies inhibit enzymatic activity of the E3 ubiquitin ligase CHIP via multiple mechanisms Open
View article: Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus-M<sup>Pro</sup>inhibitors with potent in vivo efficacy
Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus-M<sup>Pro</sup>inhibitors with potent in vivo efficacy Open
The main protease (M Pro ) of SARS-CoV-2 is crucial for viral replication and is the target of nirmatrelvir (the active ingredient of Paxlovid) and ensitrelvir. The identification of new agents with differentiated pharmacokinetic and drug …
View article: Data from Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies
Data from Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies Open
Antibody-based therapies have emerged as a powerful strategy for the management of diverse cancers. Unfortunately, tumor-specific antigens remain challenging to identify and target. Recent work established that inhibitor-modified peptide a…
View article: Supplementary Data from Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies
Supplementary Data from Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies Open
Supplemental Data and Figures
View article: Large library docking and biophysical analysis of small molecule TMPRSS2 inhibitors
Large library docking and biophysical analysis of small molecule TMPRSS2 inhibitors Open
Transmembrane protease, serine -2 (TMPRSS2) is an essential host entry factor in human airways for SARS-CoV-2 and influenza A/B and has presented as a target for antiviral drug development; however, no clinically viable, oral small molecul…
View article: Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies
Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies Open
Antibody-based therapies have emerged as a powerful strategy for the management of diverse cancers. Unfortunately, tumor-specific antigens remain challenging to identify and target. Recent work established that inhibitor-modified peptide a…
View article: Interactions with regulatory antibodies modulate CHIP E3 ubiquitin ligase‐driven tau clearance
Interactions with regulatory antibodies modulate CHIP E3 ubiquitin ligase‐driven tau clearance Open
Background The direct and chaperone‐associated interactions of E3 ubiquitin ligase CHIP with tau in Alzheimer’s disease and other tauopathies, regulates tau turnover, by directly linking it to ubiquitination and proteasomal degradation, as…
View article: Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP
Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP Open
View article: Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to <scp>HGFA</scp>, matriptase, and hepsin
Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to <span>HGFA</span>, matriptase, and hepsin Open
Inhibition of the proteolytic processing of hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP) is an attractive approach for the drug discovery of novel anticancer therapeutics which prevent tumor progression and metas…
View article: Structural basis of prostaglandin efflux by MRP4
Structural basis of prostaglandin efflux by MRP4 Open
View article: Preparing for the next pandemic
Preparing for the next pandemic Open
New lead drugs to treat COVID-19 are beginning to emerge
View article: Proteases influence colony aggregation behavior in Vibrio cholerae
Proteases influence colony aggregation behavior in Vibrio cholerae Open
View article: Rare antibody phage isolation and discrimination (RAPID) biopanning enables identification of high-affinity antibodies against challenging targets
Rare antibody phage isolation and discrimination (RAPID) biopanning enables identification of high-affinity antibodies against challenging targets Open
In vitro biopanning platforms using synthetic phage display antibody libraries have enabled the identification of antibodies against antigens that were once thought to be beyond the scope of immunization. Applying these methods against cha…
View article: Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer
Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer Open
The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precurso…
View article: A soybean rust effector protease suppresses host immunity and cleaves a 3-deoxy-7-phosphoheptulonate synthase
A soybean rust effector protease suppresses host immunity and cleaves a 3-deoxy-7-phosphoheptulonate synthase Open
The devastating soybean rust (SBR) pathogen, Phakopsora pachyrhizi , encodes many secreted proteins, but only two have been functionally characterized for their roles in rust virulence. Here, we demonstrate that transient expression of P. …
View article: Phosphorylation of a Cleaved Tau Proteoform at a Single Residue Inhibits Binding to the E3 Ubiquitin Ligase, CHIP
Phosphorylation of a Cleaved Tau Proteoform at a Single Residue Inhibits Binding to the E3 Ubiquitin Ligase, CHIP Open
Microtubule-associated protein tau (MAPT/tau) accumulates in a family of neurodegenerative diseases, including Alzheimer’s disease (AD). In disease, tau is aberrantly modified by post-translational modifications (PTMs), including hyper-pho…
View article: A Prototype Assay Multiplexing SARS-CoV-2 3CL-Protease and Angiotensin-Converting Enzyme 2 for Saliva-Based Diagnostics in COVID-19
A Prototype Assay Multiplexing SARS-CoV-2 3CL-Protease and Angiotensin-Converting Enzyme 2 for Saliva-Based Diagnostics in COVID-19 Open
With the current state of COVID-19 changing from a pandemic to being more endemic, the priorities of diagnostics will likely vary from rapid detection to stratification for the treatment of the most vulnerable patients. Such patient strati…
View article: Large library docking for novel <scp>SARS‐CoV</scp> ‐2 main protease non‐covalent and covalent inhibitors
Large library docking for novel <span>SARS‐CoV</span> ‐2 main protease non‐covalent and covalent inhibitors Open
Antiviral therapeutics to treat SARS‐CoV‐2 are needed to diminish the morbidity of the ongoing COVID‐19 pandemic. A well‐precedented drug target is the main viral protease (M Pro ), which is targeted by an approved drug and by several inve…
View article: The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT)
The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT) Open
Hyper-phosphorylated tau accumulates as insoluble fibrils in Alzheimer's disease (AD) and related dementias. The strong correlation between phosphorylated tau and disease has led to an interest in understanding how cellular factors discrim…
View article: Correction: Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases
Correction: Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases Open
View article: Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase
Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase Open
Fragment antigen-binding domains of antibodies (Fabs) are powerful probes of structure-function relationships of assembly line polyketide synthases (PKSs). We report the discovery and characterization of Fabs interrog…
View article: Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors
Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors Open
We identified several novel and previously described genes associated with FSGS progression. Targeted blockade of suPAR and CD40 pathways with novel human antibodies showed inhibition of podocyte injury in FSGS.