A5056542055- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Radioactive element chemistry and processing
- Chemical Synthesis and Analysis
- RNA Research and Splicing
- SARS-CoV-2 detection and testing
- Enzyme Structure and Function
- RNA Interference and Gene Delivery
- DNA and Nucleic Acid Chemistry
- SARS-CoV-2 and COVID-19 Research
- Amino Acid Enzymes and Metabolism
- Glycosylation and Glycoproteins Research
- Lanthanide and Transition Metal Complexes
- Advanced biosensing and bioanalysis techniques
- COVID-19 Clinical Research Studies
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Bacterial Genetics and Biotechnology
- Eosinophilic Disorders and Syndromes
- DNA Repair Mechanisms
- Respiratory viral infections research
- Radiopharmaceutical Chemistry and Applications
- Organometallic Complex Synthesis and Catalysis
- Analytical chemistry methods development
Fred Hutch Cancer Center
2015-2024
Cancer Research Center
2020
University of Washington
2016
Howard Hughes Medical Institute
2000
University of Oregon
1994-1998
University of Chicago
1987
The hairpin ribozyme catalyzes sequence-specific cleavage of RNA through transesterification the scissile phosphate. Vanadate has previously been used as a transition state mimic protein enzymes that catalyze same reaction. Comparison 2.2 angstrom resolution structure vanadate–hairpin complex with structures precursor and product complexes reveals rigid active site makes more hydrogen bonds to than or product. Because paucity functional groups capable general acid-base electrostatic...
Determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require the development well-standardized, reproducible antibody assays. This need has led to emergence a variety neutralization
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective O-atom transfer from nitrous oxide to hydride and aryl ligands of bis(pentamethylcyclopentadienyl)hafnium derivativesG. Alan Vaughan, Peter B. Rupert, Gregory L. HillhouseCite this: J. Am. Chem. Soc. 1987, 109, 18, 5538–5539Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September...
Significance The release of actinides in the environment, particularly after a nuclear power plant accident or potential use radiological dispersal device, is public health threat, as all are radioactive and will trigger damage once internalized by human body. biological chemistry actinide metal ions largely unknown new approaches to understanding pathways underlying contamination needed. This work identifies mammalian pathway for intracellular delivery toxic that actinides, through protein...
The CheY protein from Escherichia coli and Salmonella typhimurium are among the best characterized proteins of receiver domain family two component signal transduction systems in bacteria. Phosphorylation plays a central role bacterial chemotaxis. However, it is not entirely clear how its state phosphorylation contributes to function. Genetic evidence suggests that changes conformation upon phosphorylation. We present for this change by comparing NMR 15N-1H correlation spectra CheY.Mg2+...
The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of HIV envelope protein gp41. Previous attempts to elicit by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that ontogeny 4E10-equivalent responses blocked inherent autoreactivity and exceptional polyreactivity. We generated heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent recognition...
Targeted α therapy holds tremendous potential as a cancer treatment: it offers the possibility of delivering highly cytotoxic dose to targeted cells while minimizing damage surrounding healthy tissue. The metallic α-generating radioisotopes 225Ac and 227Th are promising radionuclides for therapeutic use, provided adequate chelation targeting. Here we demonstrate new chelating platform composed multidentate high-affinity oxygen-donating ligand 3,4,3-LI(CAM) bound mammalian protein...
Abstract Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition its cognate ligand, siderophore enterochelin, this protein capture transport even acidic conditions urine. Mutant LCN2 strips from...
Determinants of protective immunity against SARS-CoV-2 infection require the development well-standardized, reproducible antibody assays to be utilized in concert with clinical trials establish correlates risk and protection. This need has led appearance a variety neutralization used by different laboratories companies. Using plasma samples from COVID-19 convalescent individuals mild-to-moderate disease localized outbreak single region western US, we compared three platforms for...
The impenetrability of the blood-brain barrier (BBB) to most conventional drugs impedes treatment central nervous system (CNS) disorders. Interventions for diseases like brain cancer, neurodegeneration, or age-associated inflammatory processes require varied approaches CNS drug delivery. Cystine-dense peptides (CDPs) have drawn recent interest as drug-delivery vehicles. Found throughout phylogenetic tree, often in drug-like roles, their size, stability, and protein interaction capabilities...
Siderocalin/Lipocalin 2/Neutrophil Gelatinase Associated Lipocalin/24p3 is an innate immune system protein with bacteriostatic activity, acting by tightly binding and sequestering diverse catecholate mixed-type ferric siderophores from enteric bacteria mycobacteria. Bacterial virulence achieved through siderophore modifications, or utilization of alternate siderophores, can be explained evasion Siderocalin binding. has also been implicated in a wide variety disease processes, though often...
Abstract Targeted alpha therapy (TAT) pairs the specificity of antigen targeting with lethality particles to eradicate cancerous cells. Actinium-225 [ 225 Ac; t 1/2 = 9.920(3) days] is an alpha-emitting radioisotope driving next generation TAT radiopharmaceuticals. Despite promising clinical results, a fundamental understanding Ac coordination chemistry lags behind rest Periodic Table due its limited availability, lack stable isotopes, and inadequate systems poised probe chemical behavior...
MHC class I “ single-chain trimer ” molecules, coupling heavy chain, β 2 -microglobulin, and a specific peptide into single polypeptide are widely used in research. To more fully understand caveats associated with this design that may affect its use for basic translational studies, we evaluated set of engineered trimers combinations stabilizing mutations across eight different classical non-classical human alleles 44 peptides, including novel human/murine chimeric design. While, overall,...
Hematopoietic stem cell (HSC) gene therapy is currently performed on CD34
Mesothelin is a glypiated, cell-surface glycoprotein expressed at low levels on normal mesothelium but overexpressed by many cancers. Implicated in cell adhesion and multiple signaling pathways, mesothelin’s precise biological function overall structure remain undefined. Antibodies targeting mesothelin have been engineered into immunotoxins, antibody-drug conjugates, CAR-T cells, or bispecific T engagers as candidate therapeutics most face challenges, including binding epitopes that are not...
Mesothelin (MSLN) is a cell-surface glycoprotein expressed at low levels on normal mesothelium but overexpressed in many cancers. has been implicated to play role/s cell adhesion and multiple signaling pathways. Mucin-16/CA125 an enormous glycoprotein, also normally the progression metastasis of several cancers, directly binds mesothelin. However, precise biological function/s mesothelin mucin-16/CA125 remain mysterious. We report protein engineering recombinant production, qualitative...
Conditions and techniques that result in successful crystallization differ from RNA to RNA. However, there are some general principles facilitate of most RNAs. Three procedures were instrumental obtaining well-ordered crystals the hairpin ribozyme described this chapter. These are: i) design a series candidate constructs; ii) evaluation conditions obtain monodisperse RNA; iii) use seeding separate nucleation growth events during crystallization. can be usefully adapted for other
Cystine-dense peptides (CDPs) are a miniprotein class that can drug difficult targets with high affinity and low immunogenicity. Tools for their design, however, not as developed those small-molecule antibody drugs. CDPs have diverse taxonomic origins, but structural characterization is lacking. Here, we adapted Iterative Threading ASSEmbly Refinement (I-TASSER) Rosetta protein modeling software prediction of 4298 CDP scaffolds performed in silico prescreening binders to interest. Mammalian...