A5020025866- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Supramolecular Self-Assembly in Materials
- Molecular Junctions and Nanostructures
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Chemical Synthesis and Analysis
- Plasmonic and Surface Plasmon Research
- Metal-Organic Frameworks: Synthesis and Applications
- Enzyme Catalysis and Immobilization
- Nanofabrication and Lithography Techniques
- Advanced Biosensing Techniques and Applications
- Click Chemistry and Applications
- Hydrogels: synthesis, properties, applications
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Gold and Silver Nanoparticles Synthesis and Applications
- Diabetes Treatment and Management
- Lipid Membrane Structure and Behavior
- Innovative Microfluidic and Catalytic Techniques Innovation
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Force Microscopy Techniques and Applications
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Advanced Nanomaterials in Catalysis
Northwestern University
2008-2024
Howard Hughes Medical Institute
2007-2012
University of Chicago
2007-2011
Argonne National Laboratory
2008
Diabetes affects millions of people worldwide and the number diagnoses continues to climb annually. Though several effective medications therapeutic methods have been developed treat type 1 (T1DM) 2 (T2DM) diabetes mellitus, direct insulin injection remains only treatment for resistant (IR) patients. Here, we immobilize in a crystalline mesoporous metal-organic framework (MOF), NU-1000, obtain high loading ∼40 wt % 30 min. The acid-stable MOF capsules are found effectively prevent from...
The versatile optical and biological properties of a localized surface plasmon resonance (LSPR) sensor that responds to protein conformational changes are illustrated. detects in surface-bound construct the calcium-sensitive calmodulin. Increases calcium concentration induce 0.96 nm red shift spectral position LSPR extinction maximum (λmax). Addition chelating agent forces return its original conformation is detected as reversal λmax shift. As opposed previous work, this work demonstrates...
This work illustrates a strategy for the design of molecularly defined immunotherapies, using blend supramolecular peptide self-assembly and active site-directed protein capture.
Natural inspiration: A bioinspired functional material in the form of a hydrogel created by cross-linking an engineered version calmodulin, protein which undergoes conformational change response to ligand binding (see schematic representation), with four-armed poly(ethylene glycol) molecule terminated acrylate groups decreased volume 20 % when treated trifluoperazine. Multiple cycles gel swelling and shrinkage were possible.
A plasmonic switch based on the calcium-induced conformational changes of calmodulin is shown to exhibit reversible wavelength modulations in response changing calcium concentration. The extinction maximum (λmax) a localized surface plasmon resonance (LSPR) sensor functionalized with novel construct, cutinase−calmodulin−cutinase (CutCaMCut), reversibly shifts by 2−3 nm. high-resolution (HR) LSPR spectrometer resolution (3σ) 1.5 × 10−2 nm was developed detect these real-time, providing...
Gram-negative bacteria, especially the ones with multidrug resistance, post dire challenges to antibiotic treatments due presence of outer membrane (OM), which blocks entry many antibiotics. Current solutions for such permeability issues, namely lipophilic-cationic derivatization antibiotics and sensitization membrane-active agents, cannot effectively potentiate large, globular, hydrophilic as vancomycin, ineffective disruption OM. Here, we present our solution high-degree OM binding...
This paper describes the synthesis of giant cyclic molecules having diameters 10–20 nm. The are prepared through reactions a fusion protein building block with small molecule linkers that terminated in irreversible inhibitors enzyme domains present fusion. has N-terminal cutinase and C-terminal SnapTag react irreversibly p-nitrophenyl phosphonate (pNPP) benzylguanine (BG) groups, respectively. We use bis-BG BG-pNPP linker to join these proteins into linear structures can then bis-pNPP joins...
Enzyme-promoted assembly: The construction of a hetero-bifunctional protein building block, HaloTag–cutinase, that reacts rapidly and selectively with small-molecule linker is described. step-wise combination these blocks generates 300 kDa "megamolecule" precisely defined domain orientation, connectivity, composition.
This communication describes the design, synthesis, and biological activity of a megamolecule mimic an anti-HER2 antibody. The antibody was prepared by linking two Fabs from therapeutic trastuzumab, which are fused through heavy chain variable domain to either cutinase or SnapTag, with linker terminated in irreversible inhibitor for each enzyme. binds HER2 comparable avidity has similar cell-based assay, can arrest tumor growth mouse xenograft BT474 model. A panel 16 bivalent antibodies were...
This paper presents a solid-phase strategy to efficiently assemble multiprotein scaffolds—known as megamolecules—without the need for protecting groups and with precisely defined nanoscale architectures. The megamolecules are assembled through sequential reactions of linkers that present irreversible inhibitors enzymes fusion proteins containing enzyme domains. Here, protein an N-terminal cutinase C-terminal SnapTag domain react ethyl p-nitrophenyl phosphonate (pNPP) or chloro-pyrimidine...
This work describes the use of computational strategies to design megamolecule building blocks for self-assembly lattice networks. The megamolecules are prepared by attaching four Cutinase-SnapTag fusion proteins (CS fusions) a four-armed linker, followed functionalizing each with terpyridine linker. functionality is designed participate in metal-mediated process give article simulation-guided strategy optimize peptide linker protein conformations that best suited and therefore streamlines...
Abstract This paper describes a microfluidic chip wherein the position and order of two immobilized enzymes affects type quantity reaction products in flowing fluid. Assembly is based on self‐assembled monolayer presenting orthogonal covalent capture ligands that immobilize their respective fusion enzyme. A thiol‐tagged substrate flowed over region first enzyme—which generates product efficiently transferred to second enzyme—and enzyme's binds an adjacent thiol site chip. The amount three...
In this investigation, we report evidence for energy transfer in new protein-based megamolecules with tunable distances between donor and acceptor fluorescent proteins. The used work are monodisperse oligomers, molecular weights of ∼100-300 kDa lengths ∼5-20 nm, precisely defined structures fusion protein building blocks covalent cross-linkers. Such promising because the study complexes is usually difficult long length regime due to synthetic limitations. We incorporated proteins into...
This paper presents a method to synthetically tune atomically precise megamolecule nanobody–enzyme conjugates for prodrug cancer therapy. Previous efforts create heterobifunctional protein suffered from heterogeneity in domain stoichiometry, which part led the failure of antibody–enzyme clinical trials. We used approach synthesize anti-HER2 nanobody–cytosine deaminase with tunable numbers nanobody and enzyme domains single, covalent molecule. Linking two one improved avidity human cell line...
Die Natur als Vorbild: Ein funktionelles Material in Form eines Hydrogels wurde durch Vernetzen künstlichen Calmodulins (das auf die Bindung Liganden hin seine Konformation ändert; siehe Bild) mit einem vierarmigen Poly(ethylenglycol) endständigen Acrylatgruppen erhalten. Bei Zugabe des Trifluoperazin schrumpft das Hydrogel um 20 %. Mehrere Schwell- und Schrumpfzyklen waren möglich.
This paper describes the synthesis, characterization, and modeling of a series molecules having four protein domains attached to central core. The were assembled with "megamolecule" strategy, wherein enzymes react their covalent inhibitors that are substituted on linker. Three linkers synthesized, where each had oligo(ethylene glycol)-based arms terminated in para-nitrophenyl phosphonate group is inhibitor for cutinase. enzyme serine hydrolase reacts efficiently give new ester linkage at...
This paper describes the synthesis, characterization, and functional activity of 26 MegaMolecule-based bispecific antibody mimics for T-cell redirection toward HER2+ cancer cells. The work reports MegaMolecules that bind both receptor targets, recruit activate T-cells resulting in lysis target tumor Changing orientation linkage between Fabs against either HER2 or CD3ε results an approximately 150-fold range potency. Increasing scaffold valency from Fab dimers up to tetramers improves potency...
Site-specific modification of proteins has important applications in biological research and drug development. Reactive tags such as azide, alkyne, tetrazine have been used extensively to achieve the abovementioned goal. However, bulky side-chain "ligation scars" are often left after labeling may hinder application engineered protein products. Conjugation chemistry via dehydroalanine (Dha) provide an opportunity for "traceless" ligation because activated alkene moiety on Dha can then serve...
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