Bioconjugate Chemistry最新文献_第9页

Heterovalent Click Reactions on DNA Origami DNA折纸上的异价点击反应

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-03-05 DOI: 10.1021/acs.bioconjchem.4c0055210.1021/acs.bioconjchem.4c00552

Grant A. Knappe, Jeffrey Gorman, Andrew N. Bigley, Steven P. Harvey and Mark Bathe*,

{"title":"Heterovalent Click Reactions on DNA Origami","authors":"Grant A. Knappe, Jeffrey Gorman, Andrew N. Bigley, Steven P. Harvey and Mark Bathe*, ","doi":"10.1021/acs.bioconjchem.4c0055210.1021/acs.bioconjchem.4c00552","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00552https://doi.org/10.1021/acs.bioconjchem.4c00552","url":null,"abstract":"Nucleic acid nanoparticles (NANPs) fabricated by using the DNA origami method have broad utility in materials science and bioengineering. Their site-specific, heterovalent functionalization with secondary molecules such as proteins or fluorophores is a unique feature of this technology that drives its utility. Currently, however, there are few chemistries that enable fast, efficient covalent functionalization of NANPs with a broad conjugate scope and heterovalency. To address this need, we introduce synthetic methods to access inverse electron-demand Diels–Alder chemistry on NANPs. We demonstrate a broad conjugate scope, characterize application-relevant kinetics, and integrate this new chemistry with strain-promoted azide–alkyne cycloaddition chemistry to enable heterovalent click reactions on NANPs. We applied these chemistries to formulate a prototypical chemical countermeasure against chemical nerve agents. We envision this additional chemistry finding broad utility in the synthetic toolkit accessible to the nucleic acid nanotechnology community.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"476–485 476–485"},"PeriodicalIF":4.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641222","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

Selenalysine as a Chemical Tool for Probing Histone Post-Translational Modifications 硒赖氨酸作为探测组蛋白翻译后修饰的化学工具

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-03-05 DOI: 10.1021/acs.bioconjchem.4c0056710.1021/acs.bioconjchem.4c00567

Sandra Pinzón Martín, and , Jasmin Mecinović*,

{"title":"Selenalysine as a Chemical Tool for Probing Histone Post-Translational Modifications","authors":"Sandra Pinzón Martín,  and , Jasmin Mecinović*, ","doi":"10.1021/acs.bioconjchem.4c0056710.1021/acs.bioconjchem.4c00567","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00567https://doi.org/10.1021/acs.bioconjchem.4c00567","url":null,"abstract":"Post-translational modifications (PTMs) on histones play a crucial role in determining the structure and function of chromatin, thereby regulating the eukaryotic gene expression. Histone lysine methylation and acetylation are among the most widespread and biomedically important PTMs, with new chemical tools for their examination in high demand. Here, we report the first use of γ-selenalysine as an efficient lysine mimic for enzymatic methylation, acetylation, and deacetylation reactions catalyzed by histone lysine methyltransferases, acetyltransferases, and a deacetylase. We also show that easily accessible selenocysteine and cysteine residues can undergo chemo- and site-selective alkylation reactions to generate both unmodified and modified γ-selenalysine and related γ-thialysine residues in histone peptides. This dual-modification strategy enables the site-specific incorporation of two distinct functionalities into peptides, mimicking lysine post-translational modifications commonly found on histones. Our research presents a novel approach in which selenocysteine serves as a unique handle for the chemoselective introduction of selenalysine, along with its methylated and acetylated analogues. These tools are designed to facilitate the study of epigenetic proteins that are important for human health and disease.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"510–520 510–520"},"PeriodicalIF":4.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641254","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

FeOOH-Assisted Formation of Hybrid Polymer Nanospindles for Efficient Iron Delivery and Ferroptosis Tumor Therapy feooh辅助形成的杂化聚合物纳米纺锤体用于高效铁传递和铁下垂肿瘤治疗

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-03-05 DOI: 10.1021/acs.bioconjchem.4c0054610.1021/acs.bioconjchem.4c00546

Heng Liu, Lu Wang, Hao Jin, Kepeng Tao, Xuanqi Zhu, Mengsi Zhang, Yuchuan Hou*, Shuwei Liu* and Hao Zhang,

{"title":"FeOOH-Assisted Formation of Hybrid Polymer Nanospindles for Efficient Iron Delivery and Ferroptosis Tumor Therapy","authors":"Heng Liu, Lu Wang, Hao Jin, Kepeng Tao, Xuanqi Zhu, Mengsi Zhang, Yuchuan Hou*, Shuwei Liu* and Hao Zhang, ","doi":"10.1021/acs.bioconjchem.4c0054610.1021/acs.bioconjchem.4c00546","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00546https://doi.org/10.1021/acs.bioconjchem.4c00546","url":null,"abstract":"Exogenous iron delivery using iron-containing nanomaterials is an alternative strategy for enhancing the efficacy in ferroptosis tumor therapy but limited by the problems of low iron content, low tumor enrichment, low cellular uptake, and uncontrolled release of iron ions. To solve the problems, an FeOOH-assisted approach is demonstrated to produce iron hybrid polymer nanospindles (IHPNSs) for efficient iron delivery and ferroptosis tumor therapy. The IHPNSs are prepared through the cohydrolysis of FeCl3·6H2O with aniline, pyrrole, or amino-pyrrole. On the one hand, the hydrolysis of Fe3+ generates FeOOH particles, which further act as the templates to form fusiform architectures. On the other hand, Fe3+ triggers the oxidative polymerization of aniline, pyrrole, or amino-pyrrole. The as-prepared polymers are capable of coordinating with excessive Fe3+ and locate on the FeOOH templates, thus producing Fe3+/polymer composite-coated FeOOH nanospindles. Systematic studies indicate that the one-dimension-like morphology facilitates tumor enrichment and cellular uptake of IHPNSs. Besides the high iron content of IHPNSs, the controlled release of Fe3+ stimulated by the overexpressed glutathione (GSH) in the tumor microenvironment is achieved. The released Fe3+ is further transformed to Fe2+ by scavenging GSH, which leads to excessive accumulation of reactive oxygen species and lipid peroxides and finally induces ferroptosis of tumor cells. As a proof of concept, the IHPNSs show good efficacy in the treatment of a rat model of bladder tumors in situ.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"464–475 464–475"},"PeriodicalIF":4.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641467","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

Scalable One-Pot Production of Geranylgeranylated Proteins in Engineered Prokaryotes 工程原核生物中香叶酰化蛋白的单锅规模化生产

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-03-03 DOI: 10.1021/acs.bioconjchem.4c0049310.1021/acs.bioconjchem.4c00493

Md Shahadat Hossain, Md Mahbubul Alam, Zhiwei Huang, Faeze Mousazadeh, Ronit Sarangi, Ebbing de Jong, Kavindu C. Kolamunna, Albert L. Adhya, James L. Hougland, Atanu Acharya and Davoud Mozhdehi*,

{"title":"Scalable One-Pot Production of Geranylgeranylated Proteins in Engineered Prokaryotes","authors":"Md Shahadat Hossain, Md Mahbubul Alam, Zhiwei Huang, Faeze Mousazadeh, Ronit Sarangi, Ebbing de Jong, Kavindu C. Kolamunna, Albert L. Adhya, James L. Hougland, Atanu Acharya and Davoud Mozhdehi*, ","doi":"10.1021/acs.bioconjchem.4c0049310.1021/acs.bioconjchem.4c00493","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00493https://doi.org/10.1021/acs.bioconjchem.4c00493","url":null,"abstract":"Geranylgeranylation is a critical post-translational modification essential for various cellular functions. However, current methods for synthesizing geranylgeranylated proteins are complex and costly, which hinders access to these proteins for both biophysical and biomaterials applications. Here, we present a method for the one-pot production of geranylgeranylated proteins in Escherichia coli. We engineered E. coli to express geranylgeranyl pyrophosphate synthase (GGS), an enzyme that catalyzes the production of geranylgeranyl pyrophosphate. By coexpressing GGS with a geranylgeranyltransferase, we achieved efficient geranylgeranylation of model protein substrates, including intrinsically disordered elastin-like polypeptides (ELPs) and globular proteins such as mCherry and the small GTPases RhoA and Rap1B. We examined the biophysical behavior of the resulting geranylgeranylated proteins and observed that this modification affects the phase-separation and nanoassembly of ELPs and lipid bilayer engagement of mCherry. Taken together, our method offers a scalable, versatile, and cost-effective strategy for producing geranylgeranylated proteins, paving the way for advances in biochemical research, therapeutic development, and biomaterial engineering.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"415–423 415–423"},"PeriodicalIF":4.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.4c00493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641194","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

Molecular Determinants of Affinity and Isoform Selectivity in Protein─Small Molecule Hybrid Inhibitors of Carbonic Anhydrase 蛋白质亲和力和同工型选择性的分子决定因素──碳酸酐酶小分子杂化抑制剂

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-03-03 DOI: 10.1021/acs.bioconjchem.5c0000610.1021/acs.bioconjchem.5c00006

Sarah W. Torres, Crystal Lan, Abbigael Harthorn, Zachary Schmitz, Paul L. Blanchard, Jon Collins and Benjamin J. Hackel*,

{"title":"Molecular Determinants of Affinity and Isoform Selectivity in Protein─Small Molecule Hybrid Inhibitors of Carbonic Anhydrase","authors":"Sarah W. Torres, Crystal Lan, Abbigael Harthorn, Zachary Schmitz, Paul L. Blanchard, Jon Collins and Benjamin J. Hackel*, ","doi":"10.1021/acs.bioconjchem.5c0000610.1021/acs.bioconjchem.5c00006","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00006https://doi.org/10.1021/acs.bioconjchem.5c00006","url":null,"abstract":"Multiple studies have demonstrated the benefit of engineering hybrid ligands that combine the unique benefits of small molecules and proteins or peptides. However, the molecular complexity of hybrid ligands generates a parameter space so large it cannot be exhaustively explored. We systematically evaluated the impact of one molecular design element, conjugation site, on the discovery of functional protein-small molecule hybrids (PriSMs). We utilized a library of yeast-displayed fibronectin domain variants with amino acid and loop length diversity in the paratope and a single cysteine at one of 18 possible conjugation sites. The protein variants were coupled with maleimide-functionalized acetazolamide and sorted via competitive flow cytometry to discover potent and selective inhibitors of three isoforms of carbonic anhydrase. Deep sequencing of the resultant populations of functional PriSMs revealed an isoform-dependent distribution of conjugation site preferences. The top PriSMs showed potency and selectivity gains up to 23- and 100-fold (in this case, for CA-II vs CA-XII, with a 43-fold selectivity gain for CA-II vs CA-IX) relative to PEG2-acetazolamide alone. The presented study expands our fundamental understanding of the role of conjugation site in PriSM function and informs future PriSM engineering efforts by highlighting the benefit of conjugation site diversity in PriSM libraries.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"549–562 549–562"},"PeriodicalIF":4.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641209","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

Lysosome-Targeting Chimera Using Mannose-6-Phosphate Glycans Derived from Glyco-Engineered Yeast 利用糖工程酵母衍生的甘露糖-6-磷酸聚糖靶向溶酶体嵌合体

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-03-01 DOI: 10.1021/acs.bioconjchem.4c0051210.1021/acs.bioconjchem.4c00512

Seobin Kim, Jiyeon Kang, Danbi An, Jinho Seo* and Doo-Byoung Oh*,

{"title":"Lysosome-Targeting Chimera Using Mannose-6-Phosphate Glycans Derived from Glyco-Engineered Yeast","authors":"Seobin Kim, Jiyeon Kang, Danbi An, Jinho Seo* and Doo-Byoung Oh*, ","doi":"10.1021/acs.bioconjchem.4c0051210.1021/acs.bioconjchem.4c00512","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00512https://doi.org/10.1021/acs.bioconjchem.4c00512","url":null,"abstract":"Lysosome-targeting chimeras (LYTACs) harness the cell’s lysosomal degradation machinery to break down extracellular and membrane proteins. Previous methods used a synthetic glycopeptide containing multiple serine-O-mannose-6-phosphate (poly-M6Pn), which presented challenges such as synthetic complexity and potential immunogenicity associated with poly-M6Pn. This study introduced a LYTAC formulation, LYTACgyM6pG, which uses glyco-engineered yeast-derived mannose-6-phosphate glycans (gyM6pGs) for lysosomal transport, overcoming synthetic complexities and immunogenic risks. The gyM6pGs used in LYTACgyM6pG are human-compatible (identical to the structures found in humans) and are efficiently produced through yeast fermentation, followed by the preparation of cell wall glycans and their in vitro modifications. We employed copper-free click chemistry (azide and dibenzocyclooctyne reactions) for the robust conjugation of gyM6pGs to a nanobody targeting the immune checkpoint protein PD-L1, thereby streamlining the assembly of LYTACgyM6pG. We demonstrated that LYTACgyM6pG effectively degraded endogenous and recombinant PD-L1 proteins on the cell surface by directing them to the lysosome via the cation-independent mannose-6-phosphate receptor pathway. Furthermore, LYTACgyM6pG significantly enhanced T cell-mediated cytotoxicity against cancer cells, surpassing the efficacy of nanobodies alone. The successful application of gyM6pGs in the development of LYTACgyM6pG highlights the potential for a more viable and scalable therapeutic production of LYTACs, paving the way for broader therapeutic applications, including cancer treatment.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"424–436 424–436"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641365","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

Repurposing Lateral Flow Assays as a Versatile and Rapid Characterization Tool for Bioconjugation of Nanoparticles 重新利用横向流动试验作为纳米颗粒生物偶联的通用和快速表征工具

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-27 DOI: 10.1021/acs.bioconjchem.4c0058910.1021/acs.bioconjchem.4c00589

Bryan Gosselin, Raphael Dutour, Julie Janssens, Ivan Jabin* and Gilles Bruylants*,

{"title":"Repurposing Lateral Flow Assays as a Versatile and Rapid Characterization Tool for Bioconjugation of Nanoparticles","authors":"Bryan Gosselin, Raphael Dutour, Julie Janssens, Ivan Jabin* and Gilles Bruylants*, ","doi":"10.1021/acs.bioconjchem.4c0058910.1021/acs.bioconjchem.4c00589","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00589https://doi.org/10.1021/acs.bioconjchem.4c00589","url":null,"abstract":"This study explores the use of lateral flow assays (LFAs), recognized for their simplicity and ease-of-use, as a tool for characterizing nanoparticles functionalized with various biomolecules (e.g., proteins, antibodies, and nucleic acids). A half-strip model system was developed using ovalbumin (OVA) conjugated to gold nanoparticles (AuNPs). The characterization results obtained with LFAs were compared to those from traditional methods such as infrared spectroscopy and fluorescence labeling. The advantages of LFAs in characterizing such conjugated nanosystems were clearly demonstrated. The use of half-strip assays could not only confirm the presence of OVA on AuNPs but also enable the quantification of OVA bound per nanoparticle, offering a rapid and quantitative characterization method. Additionally, the assay showcased its versatility, as it was successfully applied to optimize the covalent coupling conditions of OVA on AuNPs, as well as to differentiate between covalently bound and adsorbed proteins. Furthermore, LFAs were employed to detect antibodies on functionalized nanoparticles, optimize their coupling to a newly developed organic coating, and confirm both the grafting of nucleic acids onto the surface and their pairing with complementary strands. These findings underscore the remarkable adaptability of LFAs for characterizing diverse nanoconjugates. Overall, LFAs stand out as a versatile and accessible tool for characterizing complex bioconjugated nanosystems, making them highly suitable for rapid Quality Control (QC) analysis and bioconjugation optimization.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"531–539 531–539"},"PeriodicalIF":4.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641197","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

A Near-Infrared Fluorescent Macromolecular Dye for Precise Identification of Glioblastoma Boundaries 一种用于胶质母细胞瘤边界精确识别的近红外荧光大分子染料

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-26 DOI: 10.1021/acs.bioconjchem.5c0001910.1021/acs.bioconjchem.5c00019

Jiale Si, Cheng Li, Xin Chen, Qinghao Zhou, Yueming Xue, Yuanyuan Ji*, Yansong Dong* and Zhishen Ge*,

{"title":"A Near-Infrared Fluorescent Macromolecular Dye for Precise Identification of Glioblastoma Boundaries","authors":"Jiale Si, Cheng Li, Xin Chen, Qinghao Zhou, Yueming Xue, Yuanyuan Ji*, Yansong Dong* and Zhishen Ge*, ","doi":"10.1021/acs.bioconjchem.5c0001910.1021/acs.bioconjchem.5c00019","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00019https://doi.org/10.1021/acs.bioconjchem.5c00019","url":null,"abstract":"Glioblastoma (GBM) is a highly invasive tumor with poorly defined boundaries, often leaving residual tissue after surgery, which contributes to the recurrence and poor prognosis. A critical challenge in GBM treatment is the precise identification of tumor boundaries during surgery to achieve a safe and complete resection. In this study, we present a novel near-infrared fluorescent agent, IR-PEG-cRGD, that is designed to accurately delineate GBM boundaries for surgical navigation of tumor resection. IR-PEG-cRGD is successfully prepared from the cyanine dye IR-820, which is conjugated to poly(ethylene glycol) (PEG) to prolong circulation time and enhance tumor accumulation. Additionally, a glioma-targeting peptide (cRGD, cyclo(Arg-Gly-Asp-d-Phe-Cys)) is conjugated to PEG to selectively target GBM. IR-PEG-cRGD demonstrates effective targeting and enrichment in subcutaneous human-derived GBM mice models, enabling specific distinguishing of the GBM margin from the surrounding parenchyma with a high signal-to-background ratio (SBR) of 4.79. Moreover, IR-PEG-cRGD can pass across the blood–brain barrier (BBB) efficiently. These findings indicate that IR-PEG-cRGD can serve as a valuable tool for the precise intraoperative delineation of GBM boundaries, aiding in safe and complete tumor resection.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"578–587 578–587"},"PeriodicalIF":4.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641146","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

Transfection via RNA-Based Nanoparticles: Comparing Encapsulation vs Adsorption Approaches of RNA Incorporation RNA纳米颗粒转染：比较RNA包封与吸附方法

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-25 DOI: 10.1021/acs.bioconjchem.5c0002810.1021/acs.bioconjchem.5c00028

Amy E. Laturski, Maria T. Dulay, Jillian L. Perry and Joseph M. DeSimone*,

引用次数: 0

Gag HIV-1 Virus-like Particles and Extracellular Vesicles Functionalization with Spike Epitopes of SARS-CoV-2 Using a Copper-Free Click Chemistry Approach 利用无铜点击化学方法用SARS-CoV-2刺突表位Gag HIV-1病毒样颗粒和细胞外囊泡功能化

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-24 DOI: 10.1021/acs.bioconjchem.4c0055910.1021/acs.bioconjchem.4c00559

Marc García-Trujillo*, Jesús Lavado-García, Arnau Boix-Besora, Francesc Gòdia and Laura Cervera*,

{"title":"Gag HIV-1 Virus-like Particles and Extracellular Vesicles Functionalization with Spike Epitopes of SARS-CoV-2 Using a Copper-Free Click Chemistry Approach","authors":"Marc García-Trujillo*, Jesús Lavado-García, Arnau Boix-Besora, Francesc Gòdia and Laura Cervera*, ","doi":"10.1021/acs.bioconjchem.4c0055910.1021/acs.bioconjchem.4c00559","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00559https://doi.org/10.1021/acs.bioconjchem.4c00559","url":null,"abstract":"Enveloped nanoparticles such as extracellular vesicles (EVs) and virus-like particles (VLPs) have emerged as promising nanocarriers capable of transporting bioactive molecules for drug delivery and vaccination. Optimized functionalization methodologies are required to increase the functionalization levels of these nanoparticles, enhancing their performance. Here, a bioorthogonal copper-free strain-promoted azide–alkyne cycloaddition (SPAAC) reaction has been optimized to functionalize human immunodeficiency virus type 1 (HIV-1) Gag-based VLPs and EVs. The optimization process has been carried out through reaction kinetics and design of experiments (DoE) using Cy5 as a reporter molecule. The functionalization of both VLPs and EVs has been studied using super-resolution fluorescence microscopy (SRFM), revealing remarkable differences between Gag-VLPs and coproduced EVs. EVs produced by mock transfection and cell growth have been functionalized achieving a mean of 3618.63 ± 48.91 and 6498.75 ± 352.71 Cy5 molecules covalently linked per particle (Cy5cov/particle), respectively. Different nanoparticles have been functionalized with two linear B-cell epitopes from the Spike protein of SARS-CoV-2, S315–338 TSNFRVQPTESIVRFPNITNLCPF and S648–663 GCLIGAEHVNNSYECD, and analyzed by an immunoassay with sera from COVID-19 patients. The obtained results validate the selected B-cell epitopes and highlight the potential of the optimized functionalization approach for the development of nanoparticle-based vaccines.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 3","pages":"486–499 486–499"},"PeriodicalIF":4.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641519","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