Bioconjugate Chemistry最新文献

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Recent Advances in Aggregation-Induced Emission Bioconjugates.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-04-01 DOI: 10.1021/acs.bioconjchem.5c00036
Guiquan Zhang, Daming Zhou, Rong Hu, Anjun Qin, Ben Zhong Tang
{"title":"Recent Advances in Aggregation-Induced Emission Bioconjugates.","authors":"Guiquan Zhang, Daming Zhou, Rong Hu, Anjun Qin, Ben Zhong Tang","doi":"10.1021/acs.bioconjchem.5c00036","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00036","url":null,"abstract":"<p><p>Fluorescence imaging technology is playing increasing roles in modern personalized and precision medicine. Thanks to their excellent photophysical properties, organic luminogens featuring aggregation-induced emission (AIE) characteristics (AIEgens) have attracted considerable attention over the past two decades. Because of their superior biocompatibility, ease of processing and functionalization, excellent water solubility, high responsiveness, and exceptional signal-to-noise ratio (SNR) for biotargets, AIE bioconjugates, formed by covalently linking AIEgens with biomolecules, have emerged as an ideal candidate for bioapplications. In this review, we summarize the progress in preparation, properties, and application of AIE bioconjugates in the last five years. Moreover, the challenges and opportunities of AIE bioconjugates are also briefly discussed.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750151","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
Advances in the Treatment of Spinal Cord Injury with Nanozymes.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-31 DOI: 10.1021/acs.bioconjchem.5c00100
Zuohong Chen, Yili Wang, Shaofang Zhang, Huanhuan Qiao, Shuquan Zhang, Hao Wang, Xiao-Dong Zhang
{"title":"Advances in the Treatment of Spinal Cord Injury with Nanozymes.","authors":"Zuohong Chen, Yili Wang, Shaofang Zhang, Huanhuan Qiao, Shuquan Zhang, Hao Wang, Xiao-Dong Zhang","doi":"10.1021/acs.bioconjchem.5c00100","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00100","url":null,"abstract":"<p><p>Spinal cord injury (SCI) with increasing incidence can lead to severe disability. The pathological process involves complex mechanisms such as oxidative stress, inflammation, and neuron apoptosis. Current treatment strategies focusing on the relief of oxidative stress and inflammation have achieved good effects, while many problems and challenges remain such as the side effect and short half-life of the therapeutic agents. Nanozymes exhibiting good biocatalytic activities can sustainably scavenge free radicals, inhibit neuroinflammation, and protect the neurons. With high stability in physiological conditions and cost-effectiveness, the nanozymes provide a new strategy for SCI treatment. In this Review, we outline the advances of nanozymes and their enzyme-mimicking activities and highlight the progress in the intervention of SCI-adopting nanozymes. We also propose future directions and clinical translation for the nanozyme strategy against SCI.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750135","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
Introducing TAPY as a Versatile Alternative to TPP for Selective Mitochondrial Targeting in Cancer Cells.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-31 DOI: 10.1021/acs.bioconjchem.4c00554
Jean C Neto, Federico Lucantoni, Leydy V González, Eva Falomir, Juan F Miravet, Francisco Galindo
{"title":"Introducing TAPY as a Versatile Alternative to TPP for Selective Mitochondrial Targeting in Cancer Cells.","authors":"Jean C Neto, Federico Lucantoni, Leydy V González, Eva Falomir, Juan F Miravet, Francisco Galindo","doi":"10.1021/acs.bioconjchem.4c00554","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00554","url":null,"abstract":"<p><p>The understanding of diseases such as cancer and Alzheimer's, along with natural aging processes, heavily relies on the study of mitochondrial function. Optical techniques like fluorescence imaging microscopy are pivotal for this purpose, enabling precise mapping of subcellular structures, including mitochondria. In this study, we explored TAPY (triarylpyridinium) cations, a novel family of mitochondrial carriers resembling the well-known triphenylphosphonium cation (TPP). Six TAPY-bodipy (BDP) dyads were prepared and chemically characterized. Confocal Laser Scanning Microscopy (CLSM) studies demonstrated that the systems were delivered selectively to the mitochondria of cancer cells (MCF-7, A549, HT-29). Remarkably, these dyads did not target the mitochondria of normal cells (HEK-293, HMEC-1), suggesting their potential use in distinguishing cancerous cells from healthy ones. A model compound comprised of the same bodipy cargo but attached to TPP was also synthesized and tested. Notably, in preliminary comparative assays with MCF-7 cells, the dyad TAPY(OMe)-BDP outperformed the TPP derivative in mitochondrial imaging, achieving twice the final fluorescence intensity. The potential chemical diversity achievable with TAPY cations is considerable, with many derivatives being accessible starting from readily available commercial products. This implies that, based on the strategy outlined in this study, carefully optimized TAPY derivatives for targeted mitochondrial delivery could potentially be developed in the future as alternatives or complements to TPP, with the present work acting as a proof of concept.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750148","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
Aptamer- vs Fab-Conjugated Liposomes: A Comparative Study in Targeting Acute Myeloid Leukemia Cells.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-27 DOI: 10.1021/acs.bioconjchem.5c00065
Hyesoo Jin, Wooseong Noh, Kangwuk Kyung, Woon-Seok Yeo, Ye Han Song, Yong-Seok Heo, Dong-Eun Kim
{"title":"Aptamer- vs Fab-Conjugated Liposomes: A Comparative Study in Targeting Acute Myeloid Leukemia Cells.","authors":"Hyesoo Jin, Wooseong Noh, Kangwuk Kyung, Woon-Seok Yeo, Ye Han Song, Yong-Seok Heo, Dong-Eun Kim","doi":"10.1021/acs.bioconjchem.5c00065","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00065","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a hematologic malignancy characterized by uncontrolled proliferation of abnormal myeloid cells with a generally poor prognosis despite advancements in chemotherapy and stem cell transplantation. To enhance therapeutic efficacy and minimize systemic toxicity, we designed liposomal nanoparticles functionalized with two distinct targeting ligands, a DNA aptamer or fragment-antigen-binding (Fab) antibody, targeting the surface marker transmembrane glycoprotein CD33 antigen (CD33) on AML cells. Aptamer- and Fab-conjugated liposomes (Apt-Lipm and Fab-Lipm, respectively) were prepared and tested for cellular uptake by CD33-positive AML cell lines. Comparative studies revealed that Fab-Lipm exhibited significantly superior binding affinity, targeting efficiency, and cellular uptake compared with Apt-Lipm. Furthermore, we demonstrated the intracellular distribution and endocytic pathways of Fab-Lipm during the cellular uptake. This comparative study of aptamer- and Fab-conjugated liposomes suggests that the Fab-conjugated liposomal system offers enhanced precision in targeting AML cells for the development of effective therapeutic strategies against hematologic malignancies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727011","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
AIE Photosensitizer with Tuned Membrane Interactions for Effective-Gram-Negative Bacteria Elimination.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-27 DOI: 10.1021/acs.bioconjchem.5c00132
Edward Kamya, Shangzhao Yi, Zhongzhong Lu, Jincong Yan, Hewan Dawit, Shah Mehmood, Yi Cao, Renjun Pei
{"title":"AIE Photosensitizer with Tuned Membrane Interactions for Effective-Gram-Negative Bacteria Elimination.","authors":"Edward Kamya, Shangzhao Yi, Zhongzhong Lu, Jincong Yan, Hewan Dawit, Shah Mehmood, Yi Cao, Renjun Pei","doi":"10.1021/acs.bioconjchem.5c00132","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00132","url":null,"abstract":"<p><p>Photodynamic antimicrobial therapy (PDAT) for efficient bacterial infection eradication critically relies on photosensitizers (PSs) that can specifically target and disrupt bacterial membranes. However, the complex membrane architecture of Gram-negative bacteria poses a significant challenge to the efficacy of most aggregation-induced emission (AIE) PSs. Herein, we introduce TPQ, an AIE PS meticulously designed to overcome this challenge by incorporating an outer membrane disruption ability, thereby boosting PDAT efficacy against Gram-negative bacteria. TPQ demonstrated excellent microbial imaging and potent PDAT activity against both Gram-positive and Gram-negative bacteria, attributed to its inherent fluorescence, high singlet oxygen generation, and balanced electrostatic and hydrophobic interactions with bacterial membranes. Notably, TPQ achieved exceptional PDAT activity (>97% efficacy) against Gram-negative bacteria while exhibiting minimal cytotoxicity to mammalian cells. Furthermore, TPQ-mediated PDAT effectively healed <i>Escherichia coli</i>-infected wounds on mice models with assured biosafety. This work provides valuable insights into the rational design of AIE PSs and highlights the synergistic effect of membrane disruption for advancing PDAT applications, particularly against recalcitrant Gram-negative bacterial infections.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717591","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
Photochemical-Promoted Cross-Coupling Reaction of Alkyl Boronate Esters with DNA-Conjugated Aryl Bromides for DNA-Encoded Library Synthesis.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-27 DOI: 10.1021/acs.bioconjchem.4c00581
Baiyang Mu, Yiwei Zhang, Xudong Wang, Rui Jin, Weiwei Lu, Nidhal Selmi, Sixiu Liu, Avinash Bhat, Sara Pahlén, Giulia Bergonzini, Zhiqiang Duan, Yinan Song, Xiaojie Lu
{"title":"Photochemical-Promoted Cross-Coupling Reaction of Alkyl Boronate Esters with DNA-Conjugated Aryl Bromides for DNA-Encoded Library Synthesis.","authors":"Baiyang Mu, Yiwei Zhang, Xudong Wang, Rui Jin, Weiwei Lu, Nidhal Selmi, Sixiu Liu, Avinash Bhat, Sara Pahlén, Giulia Bergonzini, Zhiqiang Duan, Yinan Song, Xiaojie Lu","doi":"10.1021/acs.bioconjchem.4c00581","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00581","url":null,"abstract":"<p><p>The C(sp<sup>2</sup>)-C(sp<sup>3</sup>) cross-coupling reaction is an effective way to increase the C(sp<sup>3</sup>) content in compound collections for drug discovery, enhancing molecular diversity and offering a unique chemistry starting point. In this study, we report a mild, DNA-compatible, and off-DNA-inert photochemical cross-coupling reaction inspired by the amino radical transfer strategy. This method demonstrates broad substrate scopes for DNA-encoded library (DEL) constructions, utilizing commonly available structures on DNA and diverse alkyl boronate ester building blocks, which have not been widely applied in the current DEL chemical space.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727012","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
Evolution of Lipo-Xenopeptide Carriers for siRNA Delivery: Interplay of Stabilizing Subunits.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-25 DOI: 10.1021/acs.bioconjchem.5c00096
Mina Yazdi, Tobias Burghardt, Johanna Seidl, Ulrich Lächelt, Ernst Wagner
{"title":"Evolution of Lipo-Xenopeptide Carriers for siRNA Delivery: Interplay of Stabilizing Subunits.","authors":"Mina Yazdi, Tobias Burghardt, Johanna Seidl, Ulrich Lächelt, Ernst Wagner","doi":"10.1021/acs.bioconjchem.5c00096","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00096","url":null,"abstract":"<p><p>Although small interfering RNA (siRNA) holds immense promise for treating genetic diseases and cancers, its clinical application is constrained by instability, cellular uptake barriers, and inefficient cytosolic delivery, underscoring the need for effective delivery systems. Therefore, this study focuses on screening novel T-shaped lipo-xenopeptide (XP) nanocarriers for siRNA polyplex formulation, integrating two single succinoyl-tetraethylene pentamine (Stp) units for electrostatic interaction and tyrosine tripeptides (Y<sub>3</sub>) for aromatic stabilization, along with structural modifications such as the addition of histidine (H) with or without terminal cysteines (C), and the incorporation of various fatty acids (FAs). A systematic evaluation of siRNA binding, nanoparticle stability, and gene silencing efficiency in multiple cell lines illustrated that the novel Stp1-HC lipo-XPs carriers outperform their Stp2-HC analogs, despite having fewer cationizable Stp units. This advantage stems from increased fatty acid, Y<sub>3</sub>, and C density, which compensates for reduced electrostatic interactions. The presence of H in combination with unsaturated FAs significantly improved the functional siRNA delivery. Our findings highlight the complex interplay of electrostatic, hydrophobic, covalent, hydrogen-bonded, and aromatic interactions to achieve efficient siRNA delivery, which is best-balanced in the oleic acid-containing Stp1-HC/OleA lipo-XP, exceeding the previously best standard carrier Stp2-HC/OleA in efficiency.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707732","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
Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-24 DOI: 10.1021/acs.bioconjchem.4c00545
Valentina Greco, Valeria Lanza, Barbara Tomasello, Irina Naletova, Warren R L Cairns, Sebastiano Sciuto, Enrico Rizzarelli
{"title":"Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.","authors":"Valentina Greco, Valeria Lanza, Barbara Tomasello, Irina Naletova, Warren R L Cairns, Sebastiano Sciuto, Enrico Rizzarelli","doi":"10.1021/acs.bioconjchem.4c00545","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00545","url":null,"abstract":"<p><p>In recent years, hyaluronic acid (HA) and the natural tripeptide glycyl-l-histidyl-l-lysine (GHK), especially its copper(II) complex (GHK-Cu), individually have been shown to exert helpful properties for bone protection and regeneration. However, they are not strong enough to handle oxidative stress, hydrolytic attack, or environmental conditions. Being aware that conjugation chemistry has recently emerged as an appealing approach for generating new molecular entities capable of preserving the molecular integrity of their moieties or delaying their degradation, herein we present the synthesis of conjugates of HA with GHK (GHK-HA), at different loadings of the tripeptide. GHK-HA binds copper(II) ions and potentiates the chemical and biological properties of the two components in in vitro assays. The results highlight copper's role in promoting the expression and release of certain trophic, angiogenic, and osteogenic factors, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), as well as bone morphogenetic protein-2 (BMP-2). The protective and regenerative activities of the metal ion are related to the translocation of its intracellular chaperones Copper Chaperone for Superoxide Dismutase (CCS) and Antioxidant-1 (Atox1) to the nucleus where they act as transcription factors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690465","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
Linker Design Principles for the Precision Targeting of Oncogenic G-Quadruplex DNA with G4-Ligand-Conjugated Oligonucleotides. 利用 G4 配体共轭寡核苷酸精准靶向致癌 G-四重 DNA 的连接体设计原则。
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-20 DOI: 10.1021/acs.bioconjchem.5c00008
Alva Abrahamsson, Andreas Berner, Justyna Golebiewska-Pikula, Namrata Chaudhari, Emelie Keskitalo, Cecilia Lindgren, Marcin K Chmielewski, Sjoerd Wanrooij, Erik Chorell
{"title":"Linker Design Principles for the Precision Targeting of Oncogenic G-Quadruplex DNA with G4-Ligand-Conjugated Oligonucleotides.","authors":"Alva Abrahamsson, Andreas Berner, Justyna Golebiewska-Pikula, Namrata Chaudhari, Emelie Keskitalo, Cecilia Lindgren, Marcin K Chmielewski, Sjoerd Wanrooij, Erik Chorell","doi":"10.1021/acs.bioconjchem.5c00008","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00008","url":null,"abstract":"<p><p>G-quadruplex (G4) DNA structures are noncanonical secondary structures found in key regulatory regions of the genome, including oncogenic promoters and telomeres. Small molecules, known as G4 ligands, capable of stabilizing G4s hold promise as chemical probes and therapeutic agents. Nevertheless, achieving precise specificity for individual G4 structures within the human genome remains a significant challenge. To address this, we expand upon G4-ligand-conjugated oligonucleotides (GL-Os), a modular platform combining the stabilizing properties of G4-ligands with the sequence specificity of guide DNA oligonucleotides. Central to this strategy is the linker that bridges the G4 ligand and the guide oligonucleotide. In this study, we develop multiple conjugation strategies for the GL-Os that enabled a systematic investigation of the linker in both chemical composition and length, enabling a thorough assessment of their impact on targeting oncogenic G4 DNA. Biophysical, biochemical, and computational evaluations revealed GL-Os with optimized linkers that exhibited enhanced binding to target G4s, even under thermal or structural stress. Notably, longer linkers broadened the range of targetable sequences without introducing steric hindrance, thereby enhancing the platform's applicability across diverse genomic contexts. These findings establish GL-Os as a robust and versatile tool for the selective targeting of individual G4s. By facilitating precise investigations of G4 biology, this work provides a foundation for advancing G4-targeted therapeutic strategies and exploring their role in disease contexts.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668579","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
Bioorthogonal Chemical Engineering of rAAV Capsid: Advancing Gene Therapy Targeting Using Proteins.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-03-19 Epub Date: 2025-02-24 DOI: 10.1021/acs.bioconjchem.4c00580
Maia Marchand, Sébastien Depienne, Mohammed Bouzelha, Karine Pavageau, Roxane Peumery, Denis Loquet, Dimitri Alvarez-Dorta, Mickaël Guilbaud, Mikaël Croyal, Aurélien Dupont, Oumeya Adjali, Sébastien G Gouin, David Deniaud, Mathieu Mével
{"title":"Bioorthogonal Chemical Engineering of rAAV Capsid: Advancing Gene Therapy Targeting Using Proteins.","authors":"Maia Marchand, Sébastien Depienne, Mohammed Bouzelha, Karine Pavageau, Roxane Peumery, Denis Loquet, Dimitri Alvarez-Dorta, Mickaël Guilbaud, Mikaël Croyal, Aurélien Dupont, Oumeya Adjali, Sébastien G Gouin, David Deniaud, Mathieu Mével","doi":"10.1021/acs.bioconjchem.4c00580","DOIUrl":"10.1021/acs.bioconjchem.4c00580","url":null,"abstract":"<p><p>We report the chemical conjugation of a recombinant Adeno Associated Virus (rAAV) capsid with various functionalities, including proteins, using a bioorthogonal strategy. rAAVs were azido-coated or dibenzylcyclooctyne (DBCO)-coated by chemically modifying lysine or tyrosine residues. Lysine residues were modified using a phenyl isothiocyanate anchor, and tyrosine residues using either an aryl diazonium salt or a <i>N</i>-methyl luminol derivative. We demonstrate anchor-dependent labeling levels, as observed with biochemical assays and mass spectrometry. Strain-promoted azide-alkyne cycloaddition (SPAAC) was then implemented and evaluated on the rAAV to append functionalities such as fluorescein, biotin, and carbohydrates to the azido-coated capsids. We confirmed the efficiency of the bioorthogonal reaction and observed a stronger reactivity with dibenzylcyclooctyne (DBCO) compared to bicyclononyne (BCN). The optimized SPAAC reaction was finally used to label the viral vectors with two relevant nanobodies targeting specific immune cell receptors (CD62L and CD45). <i>In vitro</i> transduction assays conducted with one rAAV-nanobody conjugate demonstrated the promising targeting properties of these chemically modified vectors. Thus, we anticipate that this strategy will positively impact the field of rAAV capsid engineering and contribute in tissue-specific targeting for the optimization of gene therapy treatments.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"521-530"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490300","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
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