Bioconjugate Chemistry最新文献

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IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18
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引用次数: 0
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18
Raphaël Dutour,  and , Gilles Bruylants*, 
{"title":"","authors":"Raphaël Dutour,  and , Gilles Bruylants*, ","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.5c00098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429458","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
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18
Lin Zhong, Lisanne C. M. Morshuis, Michelle Koerselman, Angela Memelink, Anna Kolecka, Raimond Heukers, Theo Verrips, Marcel Karperien* and Bram Zoetebier*, 
{"title":"","authors":"Lin Zhong, Lisanne C. M. Morshuis, Michelle Koerselman, Angela Memelink, Anna Kolecka, Raimond Heukers, Theo Verrips, Marcel Karperien* and Bram Zoetebier*, ","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.5c00167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429461","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
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18
Xinyue Zhao, Jiaxuan He, Yingda Chen, Jianpei Zheng, Xuefeng Li, Ting Fu, Sitao Xie*, Xiangsheng Liu* and Weihong Tan*, 
{"title":"","authors":"Xinyue Zhao, Jiaxuan He, Yingda Chen, Jianpei Zheng, Xuefeng Li, Ting Fu, Sitao Xie*, Xiangsheng Liu* and Weihong Tan*, ","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.5c00137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429463","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
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18
Tsvetelina H. Baryakova, Chia-Chien Hsu, Laura Segatori and Kevin J. McHugh*, 
{"title":"","authors":"Tsvetelina H. Baryakova, Chia-Chien Hsu, Laura Segatori and Kevin J. McHugh*, ","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.4c00575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429455","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
Genetic Engineering of VHH Antibody Fragments for Efficient Site-Specific Conjugation to Polysaccharides. VHH抗体片段与多糖高效位点特异性偶联的基因工程。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18 Epub Date: 2025-05-23 DOI: 10.1021/acs.bioconjchem.5c00167
Lin Zhong, Lisanne C M Morshuis, Michelle Koerselman, Angela Memelink, Anna Kolecka, Raimond Heukers, Theo Verrips, Marcel Karperien, Bram Zoetebier
{"title":"Genetic Engineering of VHH Antibody Fragments for Efficient Site-Specific Conjugation to Polysaccharides.","authors":"Lin Zhong, Lisanne C M Morshuis, Michelle Koerselman, Angela Memelink, Anna Kolecka, Raimond Heukers, Theo Verrips, Marcel Karperien, Bram Zoetebier","doi":"10.1021/acs.bioconjchem.5c00167","DOIUrl":"10.1021/acs.bioconjchem.5c00167","url":null,"abstract":"<p><p>Site-selective modifications of proteins, without compromising their biological activity, are highly sought after due to their critical role in many biomedical applications. Here, we established a universal and efficient approach for site-selective conjugation of a variable domain of single-chain heavy-chain only antibody fragments (VHH) to polysaccharides using thiol-maleimide chemistry, known for its specificity and efficiency. This is achieved by genetically engineering an unpaired cysteine (Cys) residue in a C-terminal extension of VHHs. In this study, we synthesized two maleimide-functionalized polysaccharides, i.e., dextran-maleimide (Dex-Mal) and hyaluronic acid-maleimide (HA-Mal), for protein conjugation. Six distinct VHHs were selected and engineered with C-terminal extensions containing Cys residues for conjugation with Dex-Mal and HA-Mal. Conjugation efficiency varied among VHHs due to structural heterogeneity, which influenced the reactivity of the engineered Cys residues. One VHH, specific to TNFα (anti-TNFα-VHH), exhibited low conjugation efficiency (<20%); however, efficiency was fully restored when a flexible glycine-serine G<sub>4</sub>S linker was introduced between the variable domain and the C-terminal Cys tag. Additionally, incorporation of two free Cys residues in the C-terminal tail further enhanced conjugation efficiency. This work establishes a robust and versatile approach for generating protein-polysaccharide conjugates, paving the way for therapeutic and diagnostic applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1319-1328"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126219","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
Multiprotein Silencing Using WRAP-Based Nanoparticles: A Proof of Concept. 使用基于wrap的纳米颗粒实现多蛋白沉默:概念验证。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18 Epub Date: 2025-05-29 DOI: 10.1021/acs.bioconjchem.5c00069
Karidia Konate, Irène Pezzati, Karima Redjatti, Estelle Agnel, Eric Vivès, Sandrine Faure, Pascal de Santa Barbara, Prisca Boisguérin, Sébastien Deshayes
{"title":"Multiprotein Silencing Using WRAP-Based Nanoparticles: A Proof of Concept.","authors":"Karidia Konate, Irène Pezzati, Karima Redjatti, Estelle Agnel, Eric Vivès, Sandrine Faure, Pascal de Santa Barbara, Prisca Boisguérin, Sébastien Deshayes","doi":"10.1021/acs.bioconjchem.5c00069","DOIUrl":"10.1021/acs.bioconjchem.5c00069","url":null,"abstract":"<p><p>Cancer remains the leading cause of death, with chemotherapy, radiotherapy, and surgical resection being the primary treatment methods. However, chemotherapy's side effects, surgical limitations, and drug resistance present significant challenges. Small interfering RNA (siRNA) has emerged as a promising tool in cancer therapy due to its ability to silence disease-related genes selectively. Recent advancements in nonviral delivery systems, particularly cell-penetrating peptides (CPPs), have enhanced the efficacy of siRNA delivery. The use of siRNA as a therapeutic tool in cancer treatment has been reported in the literature. However, silencing only one target protein has only a minor effect on tumor cell proliferation, as previously shown for WRAP-based nanoparticles targeting cyclin-dependent kinase 4 (CDK4) in human U87 glioblastoma cells. Here, we designed a more sophisticated approach to enhance therapeutic efficacy, encapsulating multiple siRNAs targeting CDK4, cyclin D1 (CD1), and MCL-1 proteins. The siRNA cocktail, delivered via WRAP5 nanoparticles, effectively silenced these targets and reduced cell proliferation in human U87 glioblastoma cells. Furthermore, the nanoparticles also demonstrated potential therapeutic impact in gastrointestinal stromal tumors (GIST), a rare cancer characterized by its tendency to resist standard treatments. This study highlights the versatility of WRAP5 nanoparticles as a platform for personalized cancer therapy, suggesting that siRNA delivery systems may be tailored to specific cancer types for more effective treatment strategies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1218-1233"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172095","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
Gold Nanoparticles Coated with Nucleic Acids: An Overview of the Different Bioconjugation Pathways. 核酸包覆的金纳米颗粒:不同生物偶联途径的综述。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18 Epub Date: 2025-05-21 DOI: 10.1021/acs.bioconjchem.5c00098
Raphaël Dutour, Gilles Bruylants
{"title":"Gold Nanoparticles Coated with Nucleic Acids: An Overview of the Different Bioconjugation Pathways.","authors":"Raphaël Dutour, Gilles Bruylants","doi":"10.1021/acs.bioconjchem.5c00098","DOIUrl":"10.1021/acs.bioconjchem.5c00098","url":null,"abstract":"<p><p>Gold-based nanomaterials have marked the last few decades with the emergence of new medical technologies presenting unique features. For instance, the conjugation of gold nanoparticles (AuNPs) and nucleic acids has allowed the creation of nanocarriers with immense promise for gene therapy applications. Although the use of lipid particles as RNA delivery vectors has been broadly explored, this review aims to focus on the limited models reported for the conjugation of RNA with AuNPs. This is nonetheless unexpected regarding the manifold strategies existing to conjugate DNA to gold nanoparticles, which are exhaustively listed in this paper. Furthermore, new processes such as fast microwave and freezing methods have been described very recently, and it therefore seemed necessary to review these recent but promising conjugation pathways and to pick out those applicable to RNA. Indeed, RNA is considerably more attractive than DNA for therapeutic purposes, but its low stability involves numerous difficulties in the construction of effective nanodevices. However, from the many approaches developed for DNA, it turns out that just two of them are frequently used for the building of RNA delivery platforms based on gold: the salt-aging method with thiolated RNA strands and physisorption. However, both approaches present strong limitations such as the low stability of the Au-S bond and the potential cytotoxicity of polycations. To conclude, this general assessment highlights that the exploration of innovating approaches implying different chemistries is needed for the creation of more robust and shapeable AuNPs-RNA conjugates.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1133-1156"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109058","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
4'-C-Cholesterol/Pyridyl-2'-O-Methyl Uridine-Functionalized siRNA Enhances Stability and Carrier-Free Gene Silencing. 4'- c -胆固醇/吡啶-2'- o -甲基尿苷功能化siRNA增强稳定性和无载体基因沉默。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18 Epub Date: 2025-06-05 DOI: 10.1021/acs.bioconjchem.5c00079
Santanu Sar, Shalini Gupta, Gourav Das, Swrajit Nath Sharma, Deepak K, Atanu Ghosh, Siddharam Shivappa Bagale, Sumit Gangopadhyay, Surajit Sinha, Kiran R Gore
{"title":"4'-<i>C</i>-Cholesterol/Pyridyl-2'-<i>O</i>-Methyl Uridine-Functionalized siRNA Enhances Stability and Carrier-Free Gene Silencing.","authors":"Santanu Sar, Shalini Gupta, Gourav Das, Swrajit Nath Sharma, Deepak K, Atanu Ghosh, Siddharam Shivappa Bagale, Sumit Gangopadhyay, Surajit Sinha, Kiran R Gore","doi":"10.1021/acs.bioconjchem.5c00079","DOIUrl":"10.1021/acs.bioconjchem.5c00079","url":null,"abstract":"<p><p>Chemical modifications and targeted delivery through the conjugation of small molecules have transformed the potential of siRNA-based therapeutics. These advancements address key challenges, such as poor cellular uptake, low bioavailability, and limited metabolic stability, making siRNA delivery more efficient and clinically viable. Cholesterol-conjugated siRNA enables cellular uptake through lipoprotein pathways without transfection agents. In this study, we reported the synthesis of 4'-<i>C</i>-cholesterol-2'-<i>O</i>-methyl (4'-<i>C</i>-chol-2'-OMe) and 4'-<i>C</i>-methylpyridine-2'-<i>O</i>-methyl (4'-<i>C</i>-Mpy-2'-OMe) uridine conjugates via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and their incorporation at the 3'-overhangs of the siRNA duplex. A single incorporation of 4'-<i>C</i>-chol-2'-OMe or 4'-<i>C</i>-Mpy-2'-OMe uridine marginally increased the stability of the siRNA duplex. In the nuclease resistance assay, 4'-<i>C</i>-Mpy-2'-OMe modification at the penultimate position of the 3'-end of poly dT<sub>20</sub> showed significant resistance against snake venom phosphodiesterase (SVPD), 3'-specific exonucleases. Gene silencing activity using anti-<i>Renilla</i> siRNA exhibited enhanced gene silencing activity when a single modification was incorporated at the 3'-overhang of the passenger strand. Similarly, 4'-<i>C</i>-Mpy-2'-OMe modification at the 3'-overhang of the passenger strand in anti-<i>Bcl</i>-2 siRNA showed compatibility to RISC assembly and exhibited effective gene silencing against the endogenous <i>Bcl-2</i> gene. A molecular modeling study illustrated that the 4'-<i>C</i>-Mpy-2'-OMe uridine at the 3'-overhang of the guide strand shows minimal interaction with the PAZ domain of the hAgo2 protein. The dual incorporation of cholesterol modifications at the 3'-overhang of both strands resulted in 68% and 93% reductions in <i>Renilla</i> luciferase expression at 1000 nM concentration after 48 and 96 h, respectively, in a carrier-free system. This study demonstrated that C4'-cholesterol conjugation provides effective cellular uptake, high nuclease resistance, and prolonged silencing activity in carrier-free mode.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1234-1246"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232649","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
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-06-18
Peggy A. Birikorang, Dominic M. Menendez, Robert Edinger, Gary Kohanbash* and W. Barry Edwards*, 
{"title":"","authors":"Peggy A. Birikorang,&nbsp;Dominic M. Menendez,&nbsp;Robert Edinger,&nbsp;Gary Kohanbash* and W. Barry Edwards*,&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.5c00070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144355175","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
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