A5090527087- Nanoplatforms for cancer theranostics
- Photoacoustic and Ultrasonic Imaging
- Click Chemistry and Applications
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Protein Degradation and Inhibitors
- Advanced X-ray and CT Imaging
- Cancer, Stress, Anesthesia, and Immune Response
- Inflammatory mediators and NSAID effects
- Nitric Oxide and Endothelin Effects
- Erythrocyte Function and Pathophysiology
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- FOXO transcription factor regulation
- Biotin and Related Studies
- Analytical Chemistry and Sensors
- Thermography and Photoacoustic Techniques
- Hippo pathway signaling and YAP/TAZ
- Photodynamic Therapy Research Studies
- Biochemical Acid Research Studies
- Computational Drug Discovery Methods
- Electrochemical Analysis and Applications
- Vitamin C and Antioxidants Research
- Steroid Chemistry and Biochemistry
- Genetic and Kidney Cyst Diseases
Scripps Research Institute
2021-2024
Scripps (United States)
2022-2023
Scripps Institution of Oceanography
2022-2023
University of Illinois Urbana-Champaign
2017-2022
Urbana University
2020
University at Buffalo, State University of New York
2015-2016
Centrum für Integrierte Onkologie
2011
University Hospital Cologne
2011
Photoacoustic (PA) imaging is an emerging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility this technology allow for specific stimuli within live-animal models. Herein, we report design, development, evaluation a series Acoustogenic Probe(s) Nitric Oxide (APNO) ratiometric, analyte-specific nitric oxide (NO) in vivo. best probe series, APNO-5, rapidly responds NO...
Photoacoustic (PA) tomography is a noninvasive technology that utilizes near-infrared (NIR) excitation and ultrasonic detection to image biological tissue at centimeter depths. While several activatable small-molecule PA sensors have been developed for various analytes, the use of molecules deep-tissue analyte delivery monitoring remains an underexplored area research. Herein, we describe synthesis, characterization, in vivo validation photoNOD-1 photoNOD-2, first organic,...
Photoacoustic (PA) imaging has emerged as a reliable in vivo technique for diverse biomedical applications ranging from disease screening to analyte sensing. Most contemporary PA agents employ NIR-I light (650–900 nm) generate an ultrasound signal; however, there is significant interference endogenous biomolecules such hemoglobin that are active this window. Transitioning longer excitation wavelengths (i.e., NIR-II) reduces the background and facilitates detection of low abundance targets...
Systematic optimization of the aza-BODIPY dye platform facilitated planarization and a red-shift in absorbance. SR-APNO-3 enabled first validated detection cancer-derived nitric oxide with PA imaging.
Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO's contributions to cancer are of particular interest due its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities NO response the nascent tumor. However, it is believed that this fades over time reaches concentration supports tumor microenvironment (TME). These complex dynamics further complicated by other factors, such as diet oxygenation, making challenging establish...
Pioneer transcription factors (TFs) exhibit a specialized ability to bind and open closed chromatin, facilitating engagement by other regulatory involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation cells. Here, we report the chemical proteomic discovery of electrophilic small molecules that stereoselectively site-specifically TF, FOXA1, at cysteine (C258) within forkhead DNA-binding domain. We show these...
The peptide natural product nisin has been used as a food preservative for 6 decades with minimal development of resistance. Nisin contains the unusual amino acids dehydroalanine and dehydrobutyrine, which are posttranslationally installed by class I lanthipeptide dehydratases (LanBs) on linear substrate through an glutamyl-tRNA–dependent dehydration Ser Thr. To date, little is known about how LanBs catalyze transfer glutamate from charged tRNA Glu to substrate, or they carry out subsequent...
The kinetic parameters for activation of yeast triosephosphate isomerase (ScTIM), orotidine monophosphate decarboxylase (ScOMPDC), and human liver glycerol 3-phosphate dehydrogenase (hlGPDH) catalysis reactions their respective phosphodianion truncated substrates are reported the following oxydianions: HPO3(2-), FPO3(2-), S2O3(2-), SO4(2-) HOPO3(2-). Oxydianions bind weakly to these unliganded enzymes tightly transition state complex (E·S(‡)), with intrinsic oxydianion Gibbs binding free...
Cyclooxygenase-2 (COX-2) overexpression is prominent in inflammatory diseases, neurodegenerative disorders, and cancer. Directly monitoring COX-2 activity within its native environment poses an exciting approach to account for illuminate the effect of local environments on protein activity. Herein, we report development CoxFluor, first activity-based sensing live cells with confocal microscopy flow cytometry. CoxFluor strategically links a natural substrate dye precursor engage both...
We report pH rate profiles for kcat and Km the isomerization reaction of glyceraldehyde 3-phosphate catalyzed by wildtype triosephosphate isomerase (TIM) from three organisms ten mutants TIM; and, Ki inhibition this phosphoglycolate trianion (I3–). The show that binding I3– to TIM (E) form EH·I3– is accompanied uptake a proton carboxylate side-chain E165, whose function abstract substrate. complexes several exist mainly as E–·I3– at high pH, in which cases define pKa deprotonation EH·I3–....
Kinetic parameters are reported for the reactions of whole substrates (kcat/Km, M(-1) s(-1)) (R)-glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) substrate pieces [(kcat/Km)E·HPi/Kd, M(-2) s(-1)] glycolaldehyde (GA) phosphite dianion (HPi) catalyzed by I172A/L232A mutant triosephosphate isomerase from Trypanosoma brucei (TbbTIM). A comparison with corresponding wild-type, I172A, L232A TbbTIM-catalyzed shows that effect I172A mutations on ΔG(⧧) wild-type is nearly same...
Abstract Cyclooxygenase‐2 (COX‐2) overexpression is prominent in inflammatory diseases, neurodegenerative disorders, and cancer. Directly monitoring COX‐2 activity within its native environment poses an exciting approach to account for illuminate the effect of local environments on protein activity. Herein, we report development CoxFluor, first activity‐based sensing live cells with confocal microscopy flow cytometry. CoxFluor strategically links a natural substrate dye precursor engage both...
Abstract Bis vor kurzem gab es keine allgemeinen Methoden zur Abschätzung der Auswirkungen post‐translationaler Regulierung auf die Enzymaktivität. Aktivitätsbasierte Sensorik (ABS) hat sich zu einem leistungsfähigen Ansatz Beobachtung Aktivitäten von niedermolekularen Verbindungen und Enzymen in lebenden Systemen entwickelt. Erste ABS‐Beispiele wurden genutzt, um allgemeine Enzymaktivität messen, jedoch Fokus letzter Zeit zum Erhöhen Selektivität für eines einzelnen Enzyms oder einer...
Abstract Ascorbate is an important biological reductant and enzyme cofactor. Although direct detection through ascorbate‐mediated reduction possible, this approach suffers from poor selectivity due to the wide range of cellular reducing agents. To overcome limitation, we leverage potential ascorbate mediate a copper‐mediated oxidative bond cleavage ether‐caged fluorophores. The copper(II) complexes supported by {bis(2‐pyridylmethyl)}benzylamine or {bis(2‐pyridylmethyl)}(2‐methoxybenzyl)amine...
Summary Most human proteins lack chemical probes, and several large-scale generalizable small-molecule binding assays have been introduced to address this problem. How compounds discovered in such “binding-first” affect protein function, nonetheless, often remains unclear. Here, we describe a “function-first” proteomic strategy that uses size exclusion chromatography (SEC) assess the global impact of electrophilic on complexes cells. Integrating SEC data with cysteine-directed activity-based...
Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO’s contributions to cancer are of particular interest due its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities NO response the nascent tumor. However, it is believed that this fades over time reaches concentration supports tumor microenvironment (TME). These complex dynamics further complicated by other factors, such as diet oxygenation, making challenging establish...
Trotz bedeutender molekulargenetischer Fortschritte zum Verständnis der Nephronophthise (NPH) ist die zelluläre Funktion NPH-Proteine weitgehend unklar. Im Gegensatz zur polyzystischen Nierenerkrankungen sind Nieren von NPH-Patienten eher klein; Zysten finden sich am kortikomedullären Übergang und eine tubuläre Atrophie richtungsweisend. In den letzten Jahren wurde Hippo-Signalweg als zentrale Signalkaskade bei Regulation Organgröße dabei wichtigen Balance aus Zellproliferation Apoptose...