Bioconjugate Chemistry最新文献

{"title":"Self-Assembled Iron(III) Coordination Cage as an MRI-Active Carrier for a Gold(I) Drug","authors":"Priya Ranjan Sahoo, Joseph A. Spernyak, Steven G. Turowski, Janet R. Morrow","doi":"10.1021/acs.bioconjchem.4c00391","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00391","url":null,"abstract":"A T₁ MRI probe based on a self-assembled coordination cage with four iron(III) centers acts as a host for the hydrolysis product of the gold(I) anticancer drug, Au(PEt₃)Cl. ¹H NMR characterization of the gold complex encapsulated within the diamagnetic Ga(III) analog of the coordination cage is consistent with loss of chloride to give aquated gold complex, most likely [Au(PEt₃)(OH₂)]⁺ within the cage. The gold complex undergoes pH-dependent speciation changes in the Ga(III) cage and is released at mildly acidic pH from both the Ga(III) and Fe(III) cages. NMR spectroscopy studies of the encapsulated gold complex in the presence of human serum albumin (HSA) show that the gold complex remains inside of the Ga(III) cage for several hours, resisting release and binding to cysteine residues of HSA. The Fe(III) cage with encapsulated gold complex shows enhanced contrast of the vasculature and uptake into CT26 tumors in BALB/c mice as shown by MRI. The gold complex is solubilized by the iron(III) cage for intravenous injection, whereas the free complex must be injected intraperitoneally. Gold complex accumulates in the tumor for both caged and free complex over 1–48 h as measured by ex-vivo analysis. Encapsulation in the Fe(III) cage modulates the biodistribution of the gold complex in mice in comparison to the free complex, consistent with the function of the cage as a carrier.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection","authors":"Wei Liu, Sufei Zhou, Ke Yang, Di Liu, Yuxing Yan, Fangzhen Tian, Tianyi Cui, Wei Wang, Lewei Bi, Lan Li, Hao Wang, Xiao-Dong Zhang","doi":"10.1021/acs.bioconjchem.4c00396","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00396","url":null,"abstract":"Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modular Semisynthetic Approach to Generate T Cell-Dependent Bispecific Constructs from Recombinant IgG1 Antibodies","authors":"Irene Shajan, Léa N. C. Rochet, Shannon R. Tracey, Rania Benazza, Bianka Jackowska, Oscar Hernandez-Alba, Sarah Cianférani, Christopher J. Scott, Floris L. van Delft, Vijay Chudasama, Bauke Albada","doi":"10.1021/acs.bioconjchem.4c00309","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00309","url":null,"abstract":"Redirecting T cells to tumor cells by bispecific antibodies is an effective approach to treat cancer, and T cell-dependent bispecific antibodies (TDBAs) are an emerging class of potent immunotherapeutic agents. By simultaneously targeting antigens on tumor cells and T cells, T cells are activated to kill tumor cells. Herein, we report a platform to generate a novel class of 2:1 structure of T cell-dependent bispecific antibody with bivalency for HER2 receptors on tumor cells and monovalency for CD3 receptors on T cells. For this, we use a biogenic inverse electron-demand Diels–Alder (IEDDA) click reaction on genetically encoded tyrosine residues to install one TCO handle on therapeutically approved antibody trastuzumab. Subsequent TCO-tetrazine click with a tetrazine-functionalized CD3-binding Fab yields a 2:1 HER2 × CD3 TDBA that exhibits a tumor-killing capability at picomolar concentrations. Monovalency toward the CD3 receptor on T cells can lower the chances of cytokine release syndrome, which is a common side effect of such agents. Our semisynthetic approach can generate highly potent TDBA constructs in a few chemoenzymatic and synthetic steps.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thiol-Specific Linkers for the Synthesis of Oligonucleotide Conjugates via Metal-Free Thiol–Ene Click Reaction","authors":"Anna L. Malinowska, Harley L. Huynh, Andrés F. Correa-Sánchez, Sritama Bose","doi":"10.1021/acs.bioconjchem.4c00336","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00336","url":null,"abstract":"Chemical conjugation of oligonucleotides is widely used to improve their delivery and therapeutic potential. A variety of strategies are implemented to efficiently modify oligonucleotides with conjugating partners. The linkers typically used for oligonucleotide conjugation have limitations in terms of stability or ease of synthesis, which generates the need for providing new improved linkers for oligonucleotide conjugation. Herein, we report the synthesis of novel vinylpyrimidine phosphoramidite building blocks, which can be incorporated into an oligonucleotide by standard solid-phase synthesis in an automated synthesizer. These linker-bearing oligonucleotides can be easily conjugated in a biocompatible manner with thiol-functionalized molecules leading to the efficient generation of oligonucleotide conjugates.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facile Rebridging Conjugation Approach to Attain Monoclonal Antibody-Targeted Nanoparticles with Enhanced Antigen Binding and Payload Delivery","authors":"Bayan Alkhawaja, Duaa Abuarqoub, Mohammad Al-natour, Walhan Alshaer, Qasem Abdallah, Ezaldeen Esawi, Malak Jaber, Nour Alkhawaja, Bayan Y. Ghanim, Nidal Qinna, Andrew G. Watts","doi":"10.1021/acs.bioconjchem.4c00275","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00275","url":null,"abstract":"Adopting conventional conjugation approaches to construct antibody-targeted nanoparticles (NPs) has demonstrated suboptimal control over the binding orientation and the structural stability of monoclonal antibodies (mAbs). Hitherto, the developed antibody-targeted NPs have shown proof of concept but lack product homogeneity, batch-to-batch reproducibility, and stability, precluding their advancement toward the clinic. To circumvent these limitations and advance toward clinical application, herein, a refined approach based on site-specific construction of mAb-immobilized NPs will be appraised. Initially, the conjugation of atezolizumab (anti-PDL1 antibody, Amab) with polymeric NPs was developed using bis-haloacetamide (BisHalide) rebridging chemistry, followed by click chemistry (NP-Fab BisHalide Ab and NP-Fc BisHalide Ab). For comparison purposes, mAb-immobilized NPs developed utilizing conventional conjugation methods, namely, <i>N</i>-hydroxysuccinimide (NHS) coupling and maleimide chemistry (NP-NHS Ab and NP-Mal Ab), were included. Next, flow cytometry and confocal microscopy experiments evaluated the actively targeted NPs (loaded with fluorescent dye) for cellular binding and uptake. Our results demonstrated the superior and selective binding and uptake of NP-Fab BisHalide Ab and NP-Fc BisHalide Ab into EMT6 cells by 19-fold and 13-fold, respectively. To evaluate the PDL1-dependent cell uptake and the selectivity of the treatments, a blocking step of the PDL1 receptor with Amab was performed prior to incubation with NP-Fab BisHalide Ab and NP-Fc BisHalide Ab. To our delight, the binding and uptake of fluorescent NPs were reduced significantly by 3-fold for NP-Fab BisHalide Ab, demonstrating the PDL1-mediated uptake. Moreover, NP-Fab BisHalide Ab and NP-Fc BisHalide Ab were entrapped with the paclitaxel payload, and their cytotoxicity was evaluated. They showed significant enhancements compared to free paclitaxel and NP-NHS Ab. Overall, this work will provide a facile conjugation method that could be implemented to actively target NPs with a plethora of therapeutic mAbs approved for various malignancies.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"234 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scission-Enhanced Molecular Imaging (SEMI)","authors":"Jeremy M. Quintana, Jonathan C. T. Carlson, Ella Scott, Thomas S. C. Ng, Miles A. Miller, Ralph Weissleder","doi":"10.1021/acs.bioconjchem.4c00337","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00337","url":null,"abstract":"Positron emission tomography (PET) imaging methods have advanced our understanding of human biology, while targeted radiotherapeutic drug treatments are now routinely used clinically. The field is expected to grow considerably based on an expanding repertoire of available affinity ligands, radionuclides, conjugation chemistries, and their FDA approvals. With this increasing use, strategies for dose reduction have become of high interest to protect patients from unnecessary and off-target toxicity. Here, we describe a simple and powerful method, scission-enhanced molecular imaging (SEMI). The technique allows for rapid corporeal elimination of radionuclides once imaging or theranostic treatment is completed and relies on “click-to-release” bioorthogonal linkers.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}