Bioconjugate Chemistry最新文献

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Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2025-01-27 DOI: 10.1021/acs.bioconjchem.4c00522
Alina D Peshkova, Taylor V Brysgel, Parth Mody, Jia Nong, Zhicheng Wang, Jacob W Myerson, Rustem I Litvinov, John W Weisel, Jacob S Brenner, Patrick M Glassman, Oscar A Marcos-Contreras, Vladimir R Muzykantov
{"title":"Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.","authors":"Alina D Peshkova, Taylor V Brysgel, Parth Mody, Jia Nong, Zhicheng Wang, Jacob W Myerson, Rustem I Litvinov, John W Weisel, Jacob S Brenner, Patrick M Glassman, Oscar A Marcos-Contreras, Vladimir R Muzykantov","doi":"10.1021/acs.bioconjchem.4c00522","DOIUrl":"10.1021/acs.bioconjchem.4c00522","url":null,"abstract":"<p><p>Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119. The goal of this study was to characterize the activity of the FIX-Ter119 conjugate and efficacy of its loading on RBCs, as well as to investigate the biodistribution, pharmacokinetics, and various biological properties of the loaded RBCs. Mouse RBCs were incubated with the Ter119-FIX conjugate, where adding 10,000 molecules per RBC resulted in 37% binding (4K/RBC), and 50,000 molecules per RBC resulted in 34% binding (17K/RBC). The pharmacokinetics (PK) profile showed that more than 90% of the Ter119-FIX conjugate was associated with RBCs and circulated stably bound to the RBCs for 24 h, increasing the area under the PK curve 7.6 times vs free FIX. Ter119-FIX loaded RBCs have specific procoagulant FIXa activity, including promotion of thrombin generation and acceleration of clotting in FIX-deficient plasma. Morphological characterization shows that Ter119-FIX-loaded RBCs undergo a shape change, with an increased fraction of echinocytes and spheroidal RBCs. Ektacytometry and electron microscopy assessment of RBC compressibility reveal a dose-dependent reduction in the deformability of RBCs loaded with Ter119-FIX. In conclusion, RBCs loaded with Ter119-FIX have the potential to serve as prohemostatic agents, but their reduced deformability warrants further engineering of Ter119-FIX to improve the safety profile.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"263-275"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanoscale Effects in the Room-Temperature UV-Visible Photoluminescence from Silica Particles and Its Cancer Cell Imaging.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2025-01-29 DOI: 10.1021/acs.bioconjchem.4c00420
Divya Rani, Deepika Singh, Anil Kumar, Monika Dhiman, Anjali Saini, Partho Biswas, Rachana Rachana, Partha Roy, Mrinal Dutta, Arup Samanta
{"title":"Nanoscale Effects in the Room-Temperature UV-Visible Photoluminescence from Silica Particles and Its Cancer Cell Imaging.","authors":"Divya Rani, Deepika Singh, Anil Kumar, Monika Dhiman, Anjali Saini, Partho Biswas, Rachana Rachana, Partha Roy, Mrinal Dutta, Arup Samanta","doi":"10.1021/acs.bioconjchem.4c00420","DOIUrl":"10.1021/acs.bioconjchem.4c00420","url":null,"abstract":"<p><p>Silica nano/microparticles have generated significant interest for the past decades, emerging as a versatile material with a wide range of applications in photonic crystals, bioimaging, chemical sensors, and catalysis. This study focused on synthesizing silica nano/microparticles ranging from 20 nm to 1.2 μm using the Stöber and modified Stöber methods. The particles exhibited photoluminescence emission across a UV-visible range, specifically in the UV (∼290, ∼327, ∼339, and ∼377 nm), blue (∼450 nm), green (∼500 nm), yellow (∼576 nm), and red (∼634 nm) range of the electromagnetic spectrum. These emissions are due to radiative relaxation processes involving oxygen-deficient centers arising due to unrelaxed oxygen vacancies, strong interacting surface silanols, 2-fold coordinated silicon, self-trapped excitons, hydrogen-related species, strain-induced defects, and nonbridging oxygen hole centers excited via two-photon and single photon absorption. The increased PL intensity with a decreasing particle size was attributed to higher concentrations of defect sites in the case of smaller-sized particles. The MTT assay, AO/EB staining, and the DCFDA assay confirmed the biocompatible nature of silica particles in the HepG2 cell line. In addition, the cell viability assay in a normal cell line (HEK293) also showed no substantial cell death. Successful bioimaging of HepG2 cells was performed with silica nano/microparticles, which exhibited blue and green fluorescence, along with Hoechst33258 dye. Even though 20 nm-sized silica particles showed higher PL emission, particles sized above 20 nm showed better fluorescence in HepG2 cells, citing their potential in <i>in vitro</i> bioimaging applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"203-215"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Effect of the Size of Gold Nanoparticle Contrast Agents on CT Imaging of the Gastrointestinal Tract and Inflammatory Bowel Disease. 纳米金造影剂粒径对胃肠道及炎症性肠病CT成像的影响
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2025-01-09 DOI: 10.1021/acs.bioconjchem.4c00507
Derick N Rosario-Berríos, Amanda Pang, Leening P Liu, Portia S N Maidment, Johoon Kim, Seokyoung Yoon, Lenitza M Nieves, Katherine J Mossburg, Andrew Adezio, Peter B Noël, Elizabeth M Lennon, David P Cormode
{"title":"The Effect of the Size of Gold Nanoparticle Contrast Agents on CT Imaging of the Gastrointestinal Tract and Inflammatory Bowel Disease.","authors":"Derick N Rosario-Berríos, Amanda Pang, Leening P Liu, Portia S N Maidment, Johoon Kim, Seokyoung Yoon, Lenitza M Nieves, Katherine J Mossburg, Andrew Adezio, Peter B Noël, Elizabeth M Lennon, David P Cormode","doi":"10.1021/acs.bioconjchem.4c00507","DOIUrl":"10.1021/acs.bioconjchem.4c00507","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. Contrast agents that provide enhanced imaging performance are highly valuable in this field. Recent studies have made significant progress in developing better contrast agents for imaging the gastrointestinal tract using nanoparticles. However, the impact of nanoparticle size on this application remains unexplored. Gold nanoparticles (AuNPs) serve as an ideal model to investigate the effect of nanoparticle size on imaging of the gastrointestinal tract due to their controllable synthesis across a broad size range. In this study, we synthesized AuNPs with core sizes ranging from 5 to 75 nm to examine the effect of the size in this setting. AuNPs were coated with poly(ethylene glycol) (PEG) to enhance stability and biocompatibility. In vitro tests show that gold nanoparticles are cytocompatible with macrophage cells (∼100% cell viability) and remain stable under acidic conditions, with no significant size changes over time. Phantom imaging studies using a clinical CT scanner indicated that there was no effect of nanoparticle size on CT contrast production, as previously demonstrated. <i>In vivo</i> imaging using a mouse model of acute colitis revealed a strong contrast generation throughout the GI tract for all agents tested. For the most part, <i>in vivo</i> contrast was independent of AuNP size, although AuNP outperformed iopamidol (a clinically approved control agent). In addition, differences in attenuation trends were observed between healthy and colitis mice. We also observed almost complete clearance at 24 h of all formulations tested (less than 0.7% ID/g was retained), supporting their value as a model platform for studying nanoparticle behavior in imaging. In conclusion, this study highlights the potential of nanoparticles as effective contrast agents for CT imaging of the gastrointestinal tract (GIT) in the UC. Further systemic research is needed to explore contrast agents that can specifically image disease processes in this disease setting.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"233-244"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Delivery of Tempol from Polyurethane Nanocapsules to Address Oxidative Stress Post-Injury.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2025-02-08 DOI: 10.1021/acs.bioconjchem.4c00360
Temitope Ale, Tolulope Ale, Kimberly J Baker, Kameel M Zuniga, Jack Hutcheson, Erin Lavik
{"title":"Delivery of Tempol from Polyurethane Nanocapsules to Address Oxidative Stress Post-Injury.","authors":"Temitope Ale, Tolulope Ale, Kimberly J Baker, Kameel M Zuniga, Jack Hutcheson, Erin Lavik","doi":"10.1021/acs.bioconjchem.4c00360","DOIUrl":"10.1021/acs.bioconjchem.4c00360","url":null,"abstract":"<p><p>Traumatic brain injuries (TBIs) result in significant morbidity and mortality due to the cascade of secondary injuries involving oxidative stress and neuroinflammation. The development of effective therapeutic strategies to mitigate these effects is critical. This study explores the fabrication and characterization of polyurethane nanocapsules for the sustained delivery of Tempol, a potent antioxidant. The nanocapsules were designed to extend the release of Tempol over a 30-day period, addressing the prolonged oxidative stress observed post-TBI. Tempol-loaded polyurethane nanocapsules were synthesized using interfacial polymerization and nanoemulsion techniques. Two generations of nanocapsules were produced, differing in Tempol loading and PEGylation levels. The first generation, with lower Tempol loading, exhibited an average size of 159.8 ± 12.61 nm and a Z-average diameter of 771.9 ± 87.95 nm. The second generation, with higher Tempol loading, showed an average size of 141.4 ± 6.13 nm and a Z-average diameter of 560.7 ± 171.1 nm. The zeta potentials were -18.9 ± 5.02 mV and -11.9 ± 3.54 mV for the first and second generations, respectively. Both generations demonstrated the presence of urethane linkages, confirmed by Fourier Transform Infrared Spectroscopy (FTIR). Loading studies revealed Tempol concentrations of 61.94 ± 3.04 μg/mg for the first generation and 77.61 ± 3.04 μg/mg for the second generation nanocapsules. Release profiles indicated an initial burst followed by a sustained, nearly linear release over 30 days. The higher PEGylation in the second generation nanocapsules is advantageous for intravenous administration, potentially enhancing their therapeutic efficacy in TBI treatment. This study demonstrates the feasibility of using polyurethane nanocapsules for the prolonged delivery of Tempol, offering a promising approach to manage oxidative stress and improve outcomes in TBI patients. Future work will include testing these nanocapsules in vivo to determine their potential at modulating recovery from TBI.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"146-151"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
l-Asparaginase Immobilized on Nanographene Oxide as an Efficient Nanobiocatalytic Tool for Asparagine Depletion in Leukemia Cells. 纳米氧化石墨烯固定化l-天冬酰胺酶作为白血病细胞天冬酰胺耗竭的高效纳米生物催化工具。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2025-01-14 DOI: 10.1021/acs.bioconjchem.4c00518
Paulina Erwardt, Bartosz Szymczak, Marek Wiśniewski, Bartosz Maciejewski, Michał Świdziński, Janusz Strzelecki, Wiesław Nowak, Katarzyna Roszek
{"title":"l-Asparaginase Immobilized on Nanographene Oxide as an Efficient Nanobiocatalytic Tool for Asparagine Depletion in Leukemia Cells.","authors":"Paulina Erwardt, Bartosz Szymczak, Marek Wiśniewski, Bartosz Maciejewski, Michał Świdziński, Janusz Strzelecki, Wiesław Nowak, Katarzyna Roszek","doi":"10.1021/acs.bioconjchem.4c00518","DOIUrl":"10.1021/acs.bioconjchem.4c00518","url":null,"abstract":"<p><p>l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric leukemias and non-Hodgkin lymphomas; however, its usage in adult patients and other types of cancer is limited due to significant side effects and drug resistance. Recent research has explored alternative formulations and delivery methods to enhance its efficacy and minimize adverse effects. One promising approach involves the immobilization of l-ASNase onto nanostructured materials, offering improved enzymatic activity and biocompatibility of the support. We harnessed an <i>E. coli</i> l-ASNase type II preparation to develop a novel strategy of enzyme immobilization on graphene oxide (GO)-based support. We compared GO and nanographene oxide (nGO) in terms of their biocompatibility and influence on enzyme parameters. The obtained l-ASNase on the nGO nanobiocatalyst maintains enzymatic activity and increases its stability, selectively acting on K562 leukemia cells without cytotoxic influence on normal endothelial cells. In the case of treated K562 cells, we confirmed enlargement in the cell and nucleus size, disturbance in the cell cycle (interphase and metaphase), and increased apoptosis rate. The potential therapeutic possibilities of immobilized l-ASNase on leukemia cell damage are also discussed, highlighting the importance of further research in this area for advancing cancer therapy.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"253-262"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wnt-Regulated Therapeutics for Blood-Brain Barrier Modulation and Cancer Therapy. wnt调节疗法用于血脑屏障调节和癌症治疗。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2024-12-16 DOI: 10.1021/acs.bioconjchem.4c00537
Pei An, Yang Tong, Rui Mu, Liang Han
{"title":"Wnt-Regulated Therapeutics for Blood-Brain Barrier Modulation and Cancer Therapy.","authors":"Pei An, Yang Tong, Rui Mu, Liang Han","doi":"10.1021/acs.bioconjchem.4c00537","DOIUrl":"10.1021/acs.bioconjchem.4c00537","url":null,"abstract":"<p><p>The Wnt signaling pathway has a significant regulatory part in tissue development and homeostasis. Dysregulation of the Wnt signaling pathway has been associated with many diseases including cancers and various brain diseases, making this signaling pathway a promising therapeutic target for these diseases. In this review, we describe the roles of the Wnt signaling pathway in the blood-brain barrier (BBB) in intracranial tumors and peripheral tumors, from preclinical and clinical perspectives, introduce Wnt-regulated therapeutics including various types of drugs and nanomedicines as BBB modulators for brain-oriented drug delivery and as therapeutic drugs for cancer treatments, and finally discuss limitations and future perspectives for Wnt-regulated therapeutics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"136-145"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ferritin versus Liposomes: A Comparative Analysis of Protein- and Lipid-Based Drug Delivery Systems.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-19 Epub Date: 2025-02-10 DOI: 10.1021/acs.bioconjchem.4c00576
Yang Liu, Feiyan Zhu, Jiuyang He, Minmin Liang
{"title":"Ferritin versus Liposomes: A Comparative Analysis of Protein- and Lipid-Based Drug Delivery Systems.","authors":"Yang Liu, Feiyan Zhu, Jiuyang He, Minmin Liang","doi":"10.1021/acs.bioconjchem.4c00576","DOIUrl":"10.1021/acs.bioconjchem.4c00576","url":null,"abstract":"<p><p>Drug delivery systems (DDSs) are crucial for the controlled release and targeted delivery of therapeutic agents, enhancing the stability and specificity of small molecules, nucleic acids, or peptides and addressing challenges such as drug instability and poor tissue targeting, particularly in oncology. Over the past few decades, liposomes have become one of the most widely used DDSs due to their unique physicochemical properties and biocompatibility. In the 1990s, liposomes were approved by the FDA as the first nanomedicine for disease treatment. Ferritin, a natural protein with a hollow nanocage structure, shares many similarities in architecture and functionality with liposomes. As an innovative DDS, ferritin offers distinct advantages including inherent tumor-targeting capabilities and exceptional biocompatibility. Liposomes and ferritin represent, respectively, established and emerging approaches in drug delivery, both excelling in key features like encapsulation efficiency and biocompatibility, which align with the standards for pharmaceutical carriers. While liposomal formulations have been clinically used, challenges such as precision targeting remain unresolved. In contrast, although ferritins hold considerable promise for drug delivery, they have not yet been implemented in clinical practice. In this review, we provide a comprehensive analysis of ferritins and liposomes as drug delivery vehicles, evaluating their drug-loading capacities, tumor-targeting capabilities, biocompatibility, and therapeutic potential. On the basis of a comparison of their intended applications and inherent limitations in the context of current treatment strategies, ferritin is expected to be an ideal delivery vehicle for tumor-targeted therapy and a strong candidate for clinical translation in the near future.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"127-135"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Site-Specific Protein Modification via Reductive Amination of Genetically Encoded Aldehyde
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-18 DOI: 10.1021/acs.bioconjchem.4c0053810.1021/acs.bioconjchem.4c00538
Lei Zhao, Zhifen Huang, Haonan Meng, Qianzhi Liang, Xun-Cheng Su and Weimin Xuan*, 
{"title":"Site-Specific Protein Modification via Reductive Amination of Genetically Encoded Aldehyde","authors":"Lei Zhao,&nbsp;Zhifen Huang,&nbsp;Haonan Meng,&nbsp;Qianzhi Liang,&nbsp;Xun-Cheng Su and Weimin Xuan*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0053810.1021/acs.bioconjchem.4c00538","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00538https://doi.org/10.1021/acs.bioconjchem.4c00538","url":null,"abstract":"<p >Aldehyde represents an extremely useful bio-orthogonal group in chemical biology and has promoted the generation of high-quality bioconjugates in therapeutics development. However, the installation of an aldehyde group on a protein and subsequent conjugation remains technically inadequate in the aspect of site choice, substrate availability, and linkage stability. Herein, we take efforts to advance the genetic incorporation of an aldehyde-containing noncanonical amino acid in <i>E. coli</i> and then show that reductive amination could be a useful reaction in introducing various amine-containing molecules, including peptides, into a specific site of proteins.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"377–382 377–382"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of Phosphoribosyl Ubiquitin Probes Targeting Legionella Dup Enzymes
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-17 DOI: 10.1021/acs.bioconjchem.4c0054110.1021/acs.bioconjchem.4c00541
Max S. Kloet, Rishov Mukhopadhyay, Rukmini Mukherjee, Mohit Misra, Cami M. P. Talavera Ormeño, Rayman T. N. Tjokrodirijo, Paul J. Hensbergen, Peter A. van Veelen, Ivan Đikić, Aysegul Sapmaz and Gerbrand J. van der Heden van Noort*, 
{"title":"Comparison of Phosphoribosyl Ubiquitin Probes Targeting Legionella Dup Enzymes","authors":"Max S. Kloet,&nbsp;Rishov Mukhopadhyay,&nbsp;Rukmini Mukherjee,&nbsp;Mohit Misra,&nbsp;Cami M. P. Talavera Ormeño,&nbsp;Rayman T. N. Tjokrodirijo,&nbsp;Paul J. Hensbergen,&nbsp;Peter A. van Veelen,&nbsp;Ivan Đikić,&nbsp;Aysegul Sapmaz and Gerbrand J. van der Heden van Noort*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0054110.1021/acs.bioconjchem.4c00541","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00541https://doi.org/10.1021/acs.bioconjchem.4c00541","url":null,"abstract":"<p >In order to effectively replicate within a host cell, the <i>Legionella pneumophila</i> bacterium secretes effector enzymes into the cytoplasm in order to manipulate cellular host pathways including host ubiquitination. Some of these effectors, the so-called SidE-family, mediate noncanonical phosphoribosyl serine ubiquitination (PR-ubiquitination) of host substrate proteins, contributing to the recruitment of ER-remodeling proteins and the formation of a <i>Legionella</i>-containing vacuole, which is crucial in the early stages of bacterial infection. PR-ubiquitination is a dynamic process that is reversed by other <i>Legionella</i> effectors called deubiquitinases for PR-ubiquitination (Dups). We recently discovered a reactive allosteric cysteine in close proximity to the catalytic triad of DupA, which can be exploited as a target for covalent probe development. We here report on the synthesis of vinyl-sulfonate and fluoro-sulfonate warhead-containing phosphoribosyl ubiquitin probes, where the Arg42 position of ubiquitin is linked to the C1 of ribose via a native guanidinium group, and compare them to triazole-linked probes. In vitro tests on recombinant DupA and SdeA<sub>PDE</sub> revealed that these probes are able to capture the enzymes covalently. In a pull-down proteomics experiment, DupA and DupB enzymes are enriched from <i>Legionella</i>-infected cell lysates, highlighting the potential of native Arg-riboside linked probes to capture <i>Legionella</i> effector enzymes in a complex proteome.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"457–463 457–463"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.4c00541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted Delivery of TLR7 Agonists to the Tumor Microenvironment Enhances Tumor Immunity via Activation of Tumor-Resident Myeloid Cells
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-02-13 DOI: 10.1021/acs.bioconjchem.4c0053410.1021/acs.bioconjchem.4c00534
Emanuela Sega, Srikanth Kotapati, Yam B. Poudel, Qinqin Cheng, Keerthi Sadanala, Bridget Schneider, Eugene P. Chekler, Chetana Rao, Sanjeev Gangwar, Tim Sproul, Deborah Law, Miranda Broz, Pavel Strop and Sayumi Yamazoe*, 
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