Bioconjugate Chemistry最新文献

{"title":"","authors":"Karidia Konate, Irène Pezzati, Karima Redjatti, Estelle Agnel, Eric Vivès, Sandrine Faure, Pascal de Santa Barbara, Prisca Boisguérin* and Sébastien Deshayes*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144355170","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}

{"title":"Chelating [²²⁷Th]Th⁴⁺ for Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors.","authors":"Luke Wharton, Scott W McNeil, Harrison Meeres, Diduo Zhang, Aidan Ingham, Helen Merkens, Maryam Osooly, Cristina Rodríguez-Rodríguez, François Bénard, Hua Yang","doi":"10.1021/acs.bioconjchem.5c00129","DOIUrl":"10.1021/acs.bioconjchem.5c00129","url":null,"abstract":"<p><p>Targeted alpha therapy (TAT) has shown high promise for the effective treatment of advanced stage cancers. Of the proposed radionuclides for TAT, Thorium-227 represents an interesting candidate given its relatively long half-life, 18.7 days, and the cascade of short-lived, high-potency, alpha-emitting daughter progeny in its decay scheme. However, to date few chelators exist which can effectively and stably bind [²²⁷Th]Th⁴⁺ at molar activities high enough for TAT. To address this challenge, this study investigated various chelating ligands for coordination of [²²⁷Th]Th⁴⁺. H₄noneunpaX was identified as a promising chelator, demonstrating radiolabeling with [²²⁷Th]Th⁴⁺ at concentrations of 10^-6 M (A_m = 272 kBq/nmol). The coordination characteristics of [Th(noneunpaX)] have been investigated through ¹H NMR spectroscopy, mass spectrometry, and DFT calculations. In this study, we also investigate for the first time the pairing of Th-227 with a peptide-based bioconjugate and evaluate the <i>in vivo</i> biodistribution characteristics. [²²⁷Th]Th-nonenupaX-Ahx-Tyr³-TATE was prepared under mild conditions (ambient temperature, 30 min) and evaluated in NRG mice bearing AR42J xenografts as a model for pancreatic neuroendocrine tumors. The ²²⁷Th-labeled radiopeptide showed high uptake in tumors (25.8±6.2 %IA/g at 3 h p.i.) and low uptake in non-targeted organs. Although some release of Th-227 was noted in serum stability studies this was not observed <i>in vivo</i>. This ligand architecture serves as an interesting framework for future optimization, which will involve improvements to the overall stability by enhancing the rigidity of the backbone and assessing other pendent donor groups with a stronger affinity toward [²²⁷Th]Th⁴⁺. Overall, this study demonstrated for the first time the viability of using peptide-based targeting to effectively deliver Th-227 to tumor sites.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1273-1287"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951307","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}

{"title":"Design and Synthesis of an Adamantane Phosphoramidite for Programmable and Automated Oligonucleotide-Functionalization.","authors":"Yuxiang Cong, Xiaoxing Chen, Thulasiram Bathini, Gang Chen, Da Han, Yangen Huang, Ruowen Wang","doi":"10.1021/acs.bioconjchem.5c00163","DOIUrl":"10.1021/acs.bioconjchem.5c00163","url":null,"abstract":"<p><p>Solid-phase synthesis has revolutionized the programmable preparation of oligonucleotides (ONs), enabling precise gene expression modulation and expanding their applications in therapeutic and material sciences. To further enhance ON functionality, this study introduces a novel adamantane-based phosphoramidite for oligonucleotide modification. Adamantane, known for its hydrophobicity and stability, was incorporated into nucleic acid aptamers using automated synthesis. Two aptamers─Sgc8 and AS1411─were functionalized with one or two adamantane units, and the products were purified and validated using high-performance liquid chromatography and mass spectrometry. The incorporation of adamantane significantly altered the aptamers' polarity and facilitated their self-assembly with poly-β-cyclodextrin, forming stable supramolecular complexes, as demonstrated by polyacrylamide gel electrophoresis. Additionally, adamantane-modified AS1411 exhibited enhanced degradation of its target protein, nucleolin, in MCF-7 cells, suggesting potential utility in targeted protein regulation. These findings establish a versatile platform for functionalizing ONs, broadening their potential for biomedical and nanotechnological applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1311-1318"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118372","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}

{"title":"Light-Controllable PEG Hydrogel Cross-Linked by Reversibly Photodissociable Dimeric Green Fluorescent Protein pdDronpa for Drug Delivery.","authors":"Yen Thi Nguyen, Hyuck Jin Lee, Namdoo Kim","doi":"10.1021/acs.bioconjchem.5c00088","DOIUrl":"10.1021/acs.bioconjchem.5c00088","url":null,"abstract":"<p><p>Hydrogel has been widely studied as a carrier model system for drug delivery. Efficient encapsulation of drug molecules and their controlled release are important factors in the design of hydrogels to control drug release at a desired time and location. In this study, we propose a photoresponsive hydrogel with tunable mechanical properties for drug delivery. The hydrogel was synthesized by cross-linking maleimide-functionalized 4-armed polyethylene glycol (4-armed PEG-Mal) with reversibly photodissociable green fluorescent protein pdDronpa. Transitions in the physical state and/or mechanical strength of the hydrogel occurred rapidly when the cross-linking agent pdDronpa was switched off and on between the monomer and dimer states using 500 and 400 nm illumination, respectively. Optically controlled release of fluorescently labeled insulin was investigated, demonstrating the ability of this hydrogel as a potent drug delivery system.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1247-1256"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172093","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}

{"title":"","authors":"Marta Tuszynska*,&nbsp;Joanna Skopinska-Wisniewska,&nbsp;Mateusz Bartniak and Anna Bajek,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144355174","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}

{"title":"","authors":"Santanu Sar,&nbsp;Shalini Gupta,&nbsp;Gourav Das,&nbsp;Swrajit Nath Sharma,&nbsp;Deepak K,&nbsp;Atanu Ghosh,&nbsp;Siddharam Shivappa Bagale,&nbsp;Sumit Gangopadhyay,&nbsp;Surajit Sinha* and Kiran R. Gore*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429459","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}

{"title":"Preclinical Evaluation of an Integrin α_vβ₆-Targeted Photodynamic Therapy.","authors":"Hua Zhang, Tanushree Ganguly, Rebecca Harris, Ryan A Davis, Sven H Hausner, Luciana Kovacs, Julie L Sutcliffe","doi":"10.1021/acs.bioconjchem.5c00202","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00202","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is a minimally invasive treatment in which an external light source activates an injected photosensitizer (PS) to generate reactive oxygen species, causing localized cell death. Although the first PDT received FDA approval in 1995, clinical adoption has been limited, in part due to the limited tumor selectivity of PSs. The goal of this study was to develop a PS with improved tumor selectivity by incorporating a targeting peptide that selectively binds to the integrin α_vβ₆. The integrin α_vβ₆ is an epithelial-specific cell-surface receptor that is overexpressed in several cancer types, with expression level often linked to poor overall survival. The integrin α_vβ₆ targeting peptide (ABM-5G) was conjugated onto a water-soluble PS (IRDye700DX, IR700) in solution phase, and the resulting PS-α_vβ₆-targeted-peptide conjugate (IR700-ABM-5G, <b>1</b>) demonstrated excellent photochemical and photophysical properties, including high extinction coefficient and singlet oxygen productivity similar to the nontargeted PS (free IR700). <i>In vitro,</i> <b>1</b> showed α_vβ₆-selective binding to and internalization into DX3puroβ6 (α_vβ₆+) cells vs DX3puro (α_vβ₆-) cells, and α_vβ₆-selective phototoxicity with EC₅₀s of 1.6 nM for DX3puroβ6 cells and ≥ 250 nM for DX3puro cells. In mice bearing paired DX3puroβ6 (α_vβ₆+) and DX3puro (α_vβ₆-) tumor xenografts, the fluorescence intensity of <b>1</b> in DX3puroβ6 (α_vβ₆+) tumors was 2.5- to 7-fold higher than that of the other tissues (including DX3puro (α_vβ₆-) tumors, <i>p</i> < 0.0001), except for the kidneys and stomach. A single treatment of <b>1</b> (1.4 nmol per mouse) combined with near-infrared light exposure significantly suppressed the growth of DX3puroβ6 (α_vβ₆+) tumors (198 ± 112 mm³ vs 714 ± 251 mm³ for saline control, <i>p</i> < 0.0001, on day 37 post treatment). In summary, PDT treatment with <b>1</b> demonstrated α_vβ₆-selective therapeutic efficacy both <i>in vitro</i> and <i>in vivo</i> and is a promising targeted therapy for the treatment of a range of α_vβ₆-expressing cancers.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281678","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}

{"title":"Nanomaterial Applications in Prevention and Treatment Strategies of Virus: A Review.","authors":"Gao-Li Xin, Chong Zhang, Jia-Lin Ni, Yong-Kang Li, Yu Sun, Xiu-Xia He","doi":"10.1021/acs.bioconjchem.5c00170","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00170","url":null,"abstract":"<p><p>Virus infections pose significant threats to human health and have profound implications for the global economy. Traditional vaccines and antiviral drugs have several limitations in the management of viral infections. For example, the efficacy of vaccines diminishes following viral mutations, while antiviral medications are susceptible to the development of drug resistance. In recent years, nanomaterials have attracted considerable attention in antiviral research due to their physicochemical properties and biocompatibility. This article provides a systematic overview of the advancements in the antiviral application of nanomaterials. We provide a comprehensive overview of the antiviral effects of nanomaterials in various applications, including the enhancement of immune responses as vaccine carriers, improved sensitivity in virus detection, inhibition of viral infection by direct antiviral activity, enhancement of drug efficacy as drug delivery carriers, interruption of virus transmission by surface coating, and virus tracing to assist in the study of viral mechanisms. Challenges of nanomaterials in the antiviral research are also discussed.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273659","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}

{"title":"Multilayer Fluorescent Immunoassay for Early and Sensitive Dengue Virus Detection Using Host and Viral Biomarkers.","authors":"Andrew S Browne, Jieqiong Fang, Amany Elsharkawy, Tianwei Jia, Evan Reboli, Ying Luo, Xiaolin Sheng, Mukesh Kumar, Suri S Iyer","doi":"10.1021/acs.bioconjchem.5c00153","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00153","url":null,"abstract":"<p><p>Early detection and monitoring of dengue virus (DENV) infections are critical for effective disease management. A comprehensive approach combining viral and host biomarker detection improves diagnostic accuracy. Here, we describe a signal enhancement technique combining fluorescent silica nanoparticles and bioorthogonal chemistries for the ultrasensitive detection of monocyte chemoattractant protein 1 (MCP-1), interferon gamma-induced protein 10 (IP-10), and the viral biomarker nonstructural protein 1 (NS1). Our plate-based sandwich assay enhances signals with multiple layered fluorescent dye-encapsulated nanoparticles. In human serum, the assay achieved a limit of detection (LOD) of 43 pg/mL (∼5.0 nM) for MCP-1, ranging from 100 pg/mL to 100 ng/mL; 66 pg/mL (∼7.6 nM) for IP-10, ranging from 10 pg/mL to 100 ng/mL; and 351 pg/mL (8.6 nM) for NS1, ranging from 100 pg/mL to 10 μg/mL. We also monitored host biomarkers in dengue virus-infected AG129 mice using a Milliplex Mouse Cytokine/Chemokine Magnetic Bead Panel. MCP-1 levels in infected mice ranged from 1000 to 7000 pg/mL (mean: 2911 pg/mL), while uninfected controls showed much lower levels (1-10 pg/mL, mean 7 pg/mL). IP-10 levels ranged from 150 to 300 pg/mL (mean 188 pg/mL) in infected mice and 50-100 pg/mL (mean 69.4 pg/mL) in controls. These results aligned with our multilayered fluorescent assay, demonstrating its potential for sensitive dengue biomarker detection.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273658","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}

{"title":"Simple Diaminonucleoside-Mediated Nonenzymatic Ligation of Oligonucleotides.","authors":"Michael J Capperauld, Krish Kiran Valluru, Jagandeep S Saraya, Evan Zakaria, Connor E Wong, Derek K O'Flaherty","doi":"10.1021/acs.bioconjchem.5c00090","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00090","url":null,"abstract":"<p><p>Oligonucleotide-templated chemical ligation is a powerful and robust technique to covalently join two or more oligonucleotides. Chemical handles, such as amino-modifiers, can be incorporated to enhance ligation efficiency. However, their incorporation is typically laborious, expensive, and time-consuming. Utilizing 3',5'-diamino-3',5'-dideoxythymidine (or 3',5'-diamino-2',3',5'-trideoxy-5-methylcytidine) and a water-soluble condensing reagent, we demonstrate a simple and cost-effective methodology for chemically ligating two oligonucleotides containing opposing monophosphate groups in a template-directed manner. Through reaction optimization, product formation reached >85% within 4 h in DNA, RNA-like, and certain chimeric-based systems. Our methodology will find applications in chemical biology and biotechnology.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281679","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}