Bioconjugate Chemistry最新文献_第6页

Structural Optimization of Guanidinium-Linked Morpholino Phosphorodiamidate Morpholino Oligonucleotide Chimeras to Improve In Vitro Antisense Efficacy 提高体外反义效果的胍-键合氨基磷二酯寡核苷酸嵌合体结构优化。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-22 DOI: 10.1021/acs.bioconjchem.6c00176

Mohammed Qasim, Sharmeen Naaz, Subhamoy Pratihar, Swrajit Nath Sharma, Surajit Sinha

{"title":"Structural Optimization of Guanidinium-Linked Morpholino Phosphorodiamidate Morpholino Oligonucleotide Chimeras to Improve In Vitro Antisense Efficacy","authors":"Mohammed Qasim, Sharmeen Naaz, Subhamoy Pratihar, Swrajit Nath Sharma, Surajit Sinha","doi":"10.1021/acs.bioconjchem.6c00176","DOIUrl":"10.1021/acs.bioconjchem.6c00176","url":null,"abstract":"Although phosphorodiamidate morpholinooligomers (PMOs)are potentand stable antisense agents, their neutral backbone limits cellularuptake and biodistribution, requiring specialized delivery strategiesto improve therapeutic efficacy. Chimeric guanidinium-linked morpholinooligomers (GMOs) with PMOs are designed to enhance cellular deliveryyet compromise hybridization with the target sequence due to backbonerigidity. To address this, we designed flexible GMO-PMO chimeras byincorporating sarcosine, β-alanine, and ethanamine as internucleotidespacers in the oligonucleotide. Thermal melting studies on a 19-merpolythymidine (polyT) sequence demonstrate that these flexible GMO-PMOspartially restore duplex stability in a modification-dependent manner.This structural restoration is also observed in biologically relevantmixed GMO-PMO sequences targeting Nanog, a gene linkedto stemness and cancer biology, while retaining their B-type globalgeometry as confirmed by circular dichroism analysis. The optimizedethanamine-modified Nanog chimera elicited strong,dose-dependent silencing, with up to 95% repression in MCF7 and ∼73%in HCT116 cells at 1 μM after 48 h. Importantly, both rigidand flexible GMO-PMOs exhibit similar lysosomal sequestration, varyingin a cell-line-dependent manner. Collectively, flexible GMO-PMO chimerasmitigate the long-standing trade-off between carrier-free PMO deliveryand duplex stability, establishing a robust platform for antisensegene silencing and potential therapeutic applications.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1602–1610"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148546945","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

Strategies for Packaging Macromolecules onto or into Virus-Like Particles 将大分子包装到病毒样颗粒上或装入病毒样颗粒的策略

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-28 DOI: 10.1021/acs.bioconjchem.6c00172

Tariq Hussain, Marina Sicheng Xie, Carolina Pérez-Segura, Michael S. VanNieuwenhze, Jodi A. Hadden-Perilla, Adam Zlotnick

{"title":"Strategies for Packaging Macromolecules onto or into Virus-Like Particles","authors":"Tariq Hussain, Marina Sicheng Xie, Carolina Pérez-Segura, Michael S. VanNieuwenhze, Jodi A. Hadden-Perilla, Adam Zlotnick","doi":"10.1021/acs.bioconjchem.6c00172","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.6c00172","url":null,"abstract":"There is an unmet need to developvehicles for deliveringproteincargo and ribonucleoprotein complexes to cells. Virus capsids, orvirus-like particles, have numerous advantages as self-assemblingprotein platforms, but there remains a need to develop robust methodsfor the specific internal packaging of cargo. In this work, we usethe Hepatitis B Virus (HBV) capsid as our delivery vehicle. To specificallyassociate protein cargo with the capsid, we covalently attached aderivative of an HBV sulfamoylbenzamide (SBA) antiviral to green fluorescentprotein (GFP). We show that SBA-tagged GFP can associate with HBVcapsids, but efficient internal packaging requires engineering theassembly of capsids around a cargo. Under standard co-assembly conditions,SBA-tagged GFP predominantly displayed on the capsid exterior, reaching∼40 GFP cargo proteins per capsid. We tested two strategiesto drive encapsidation of protein cargo. First, remodeling the capsidinterior was nominally effective. Conversely, His-tag/Ni2+-mediated clustering converts the cargo into a multivalent capsid-bindingscaffold that templates assembly, enabling internal packaging of upto ∼30 cargo proteins per capsid. Based on capsid geometry,we suggest the practical limit is approximately 30 cargo proteinsper T = 4 HBV capsid, indicating that this strategy approaches maximalloading. Together, these results provide a highly effective methodfor packaging proteins inside VLPs.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1591–1601"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769859","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

Recent Advances and Future Directions in On-DNA Reaction Development dna上反应的最新进展及未来发展方向

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-08-01 DOI: 10.1021/acs.bioconjchem.6c00344

Xudong Wang, Xuanjing Shen, Zhiqiang Duan, Xiaojie Lu

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Preclinical Evaluation in Animals for the Efficacy, Dosimetry, and Safety of [68Ga]Ga/[177Lu]Lu-TVS-PSMA Radioligands, and First-in-Human Study of [68Ga]Ga-TVS-PSMA-1 [68Ga]Ga/[177Lu]Lu-TVS-PSMA放射配体的有效性、剂量学和安全性的动物临床前评价，以及[68Ga]Ga- tvs - psma -1的首次人体研究。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-17 DOI: 10.1021/acs.bioconjchem.6c00211

Yuduo Wan, Yang Wang, Wanlu Feng, Liping Yang, Qinghong Sun, Huanyu Chen, Ya Liu, Yan Zhu, He Zhang, Haoyuan Ding, Zibo Li, Li Wang

{"title":"Preclinical Evaluation in Animals for the Efficacy, Dosimetry, and Safety of [68Ga]Ga/[177Lu]Lu-TVS-PSMA Radioligands, and First-in-Human Study of [68Ga]Ga-TVS-PSMA-1","authors":"Yuduo Wan, Yang Wang, Wanlu Feng, Liping Yang, Qinghong Sun, Huanyu Chen, Ya Liu, Yan Zhu, He Zhang, Haoyuan Ding, Zibo Li, Li Wang","doi":"10.1021/acs.bioconjchem.6c00211","DOIUrl":"10.1021/acs.bioconjchem.6c00211","url":null,"abstract":"Toimprove the theranostic efficacy of PSMA-targeted radiopharmaceuticalson patients with medium-to-low PSMA expression, we radiolabeled aseries of novel designed PSMA-targeting dimer agents to improve tumorimaging and treatment outcomes under challenging conditions. All agentswere successfully radiolabeled with 68Ga in moderate decay-correctedlabeling yield and high radiochemical purity. Among them, [68Ga]Ga-TVS-PSMA-1 exhibited high tumor uptake in bothLNCaP and 22RV1 models. [177Lu]Lu-TVS-PSMA-1 demonstrated significantly improved treatment efficacy with a lowerdose and good safety profile compared with [177Lu]Lu-PSMA-617.A first-in-human [68Ga]Ga-TVS-PSMA-1 PET/CTscan was performed in a 66-year-old male prostate cancer patient.Two metastatic lesions in the lumbar vertebrae were clearly visualized,and the primary tumor exhibited an SUVmax of 30.3. The [68Ga]Ga-TVS-PSMA-1 showed lower salivary gland uptakecompared with previously reported values for [68Ga]Ga-PSMA-11;however, confirmation in larger patient cohorts is required. Thisstudy demonstrates that the dimer agent TVS-PSMA-1 holdsgreat potential as a next-generation theranostic agent for prostatecancer.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1633–1642"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467785","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

Lipid Nanoparticle-Based αHTRA1 mRNA Improves Pancreatic Ductal Adenocarcinoma Redox Microenvironment by Suppressing HTRA1/HIF-1 Signaling 脂质纳米颗粒αHTRA1 mRNA通过抑制HTRA1/HIF-1信号通路改善胰腺导管腺癌氧化还原微环境

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-05-12 DOI: 10.1021/acs.bioconjchem.6c00013

Xinya Zhao, Xufeng Tao, Hong Xiang, Xin Kong, Xiaonan Zhang, Yu Wu, Fangyue Guo, Deshi Dong

{"title":"Lipid Nanoparticle-Based αHTRA1 mRNA Improves Pancreatic Ductal Adenocarcinoma Redox Microenvironment by Suppressing HTRA1/HIF-1 Signaling","authors":"Xinya Zhao, Xufeng Tao, Hong Xiang, Xin Kong, Xiaonan Zhang, Yu Wu, Fangyue Guo, Deshi Dong","doi":"10.1021/acs.bioconjchem.6c00013","DOIUrl":"10.1021/acs.bioconjchem.6c00013","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a highly malignanttumorwith an inferior prognosis, and currently, there is a lack of effectivetreatment options. In immunotherapy, messenger RNA (mRNA)-based drugs,especially mRNA vaccines, have shown great potential in recent years.Previous research has found that high-temperature requirement proteinA1 (HTRA1) is upregulated in PDAC and is a key factor in disease progression.Based on this key discovery, we have developed an mRNA drug basedon lipid nanoparticles (LNP), which utilizes the efficient deliverycapability of LNP to achieve precise delivery of antibodies targetingHTRA1 in vivo, thereby directly inhibiting the expression of HTRA1in tumor cells. As a delivery carrier, LNP not only improves the stabilityand bioavailability of mRNA but also enhances its enrichment and releaseefficiency in tumor tissues. This study confirms that anti-HTRA1 (αHTRA1)mRNA can effectively inhibit the malignant phenotype of PDAC cells.Furthermore, we have established C57BL/6 wild-type (WT) and LSL-KrasG12D/+; Pdx1-Cre (KC) mousepancreatic organoid models, and the results indicate that the drug,by inhibiting the hypoxia-inducible factor-1 (HIF-1) signaling pathway,improves the tumor microenvironment and can effectively suppress theprogression of PDAC. The mRNA drugs based on LNP designed and synthesizedin this study have good therapeutic potential for PDAC, providingnew potential drugs for targeted therapy of PDAC.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1551–1561"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147924739","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

One-Pot Synthesis of Functionalized Coumarin Fluorophores Enables Rapid Access to Live-Cell Bioorthogonal Labeling and Microenvironmental Sensing Agents 一锅合成功能化香豆素荧光团使快速获得活细胞生物正交标记和微环境传感剂。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-06-30 DOI: 10.1021/acs.bioconjchem.6c00257

Pramsak Patawanich, Max J. Bedding, William G. Ryder, Richard J. Payne, Elizabeth J. New, Liam D. Adair

引用次数: 0

Guanine-Rich DNA Aptamers for Selective Binding to Agarose Hydrogels 富含鸟嘌呤的DNA适体选择性结合琼脂糖水凝胶。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-13 DOI: 10.1021/acs.bioconjchem.6c00242

Yibo Liu, Juewen Liu

{"title":"Guanine-Rich DNA Aptamers for Selective Binding to Agarose Hydrogels","authors":"Yibo Liu, Juewen Liu","doi":"10.1021/acs.bioconjchem.6c00242","DOIUrl":"10.1021/acs.bioconjchem.6c00242","url":null,"abstract":"Although DNA-functionalized hydrogels have been widelyexploredfor sensing, controlled release, and smart materials, the potentialfor strong, noncovalent recognition between DNA and hydrated polymernetworks remains largely unexplored. Here, we report the selectionof DNA aptamers that specifically bind agarose hydrogels. Using astructured DNA library and agarose beads as the target, a dominantguanine-rich sequence, Agar-1, emerged after 11 rounds of selection.Quantitative PCR and fluorescence assays confirmed that the enrichedsequences bind agarose substantially more strongly than a random DNAlibrary. Truncation yielded a 42-nucleotide aptamer that retainedbinding activity, whereas further truncation that preserved only theguanine-rich region abolished binding, indicating a strict structuralrequirement. Notably, binding required Mg2+ and was inhibitedby K+, suggesting a non-G-quadruplex recognition mechanism.In contrast to previously reported C/T-rich sequences that bind microplastics,the G-rich agarose aptamers highlight the versatility of DNA–polymerinteractions and demonstrate how simple changes in sequence compositioncan drive recognition of distinct materials. These findings establishthe feasibility of evolving aptamers against hydrogels and providea foundation for engineering programmable DNA–hydrogel interfacesfor biosensing, responsive materials, and controlled-release applications.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1657–1664"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434344","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

Differential Chemoselectivity of Homobifunctional and Monofunctional Maleimide Reagents for Bioconjugation 同双功能和单功能马来酰亚胺生物偶联试剂的差异性化学选择性

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-08-10 DOI: 10.1021/acs.bioconjchem.6c00295

Sean K. Hsu, Nicole F. Steinmetz

{"title":"Differential Chemoselectivity of Homobifunctional and Monofunctional Maleimide Reagents for Bioconjugation","authors":"Sean K. Hsu, Nicole F. Steinmetz","doi":"10.1021/acs.bioconjchem.6c00295","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.6c00295","url":null,"abstract":"Maleimides are widely utilized in bioconjugation becausethey efficientlyand selectively react with thiols. Owing to their favorable reactionkinetics, maleimides have found broad applications in bioconjugatechemistry, including the synthesis of antibody-drug conjugates forcancer therapy, fluorescence labeling of proteins, or functionalizationof materials. As increasingly complex platforms are developed, multivalentlinkers are being incorporated more frequently into synthetic strategies.Although the chemistry of monovalent maleimides is well understood,the chemoselectivity of multivalent maleimide linkers has not beenfully established. To investigate differences in the chemoselectivityof mono- and bivalent maleimides, we performed bioconjugation of mal-PEG11-mal or mPEG12-mal with the physalis mottle virus-likeparticle. Through a series of chemical assays and characterizationstudies, we demonstrate that while monovalent maleimides are highlyselective for cysteine modifications, bivalent maleimides exhibitcross-reactivity toward both lysine and cysteine residues. Overall,this study highlights how linker valency can influence the chemoselectivityof maleimide-based conjugation chemistry.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1700–1710"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769558","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

Development of a Fluorescent Probe for Real-Time In Vivo Imaging of Cysteine Dynamics in a Mouse Model of Lipopolysaccharide-Induced Acute Lung Injury 用于脂多糖诱导急性肺损伤小鼠模型半胱氨酸动态实时体内成像的荧光探针的研制

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-08-10 DOI: 10.1021/acs.bioconjchem.6c00349

Fei Gao, Kai Wang, Feng-Ming Liang, You-Zhen Feng, Zhong-Yuan Cheng

引用次数: 0

Conjugates of Heme and Intrinsically Disordered Peptides toward the Development of Synthetic Artificial Oxygen Carriers 血红素和内在无序肽偶联物在人工氧载体合成中的应用。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-07-15 Epub Date: 2026-06-29 DOI: 10.1021/acs.bioconjchem.6c00231

Yuchen Qiao, Jeffrey Wang, Matthew Chu, Chi-Kwong Chang, Myeonggon Park and Bing Xu*,

{"title":"Conjugates of Heme and Intrinsically Disordered Peptides toward the Development of Synthetic Artificial Oxygen Carriers","authors":"Yuchen Qiao, Jeffrey Wang, Matthew Chu, Chi-Kwong Chang, Myeonggon Park and Bing Xu*, ","doi":"10.1021/acs.bioconjchem.6c00231","DOIUrl":"10.1021/acs.bioconjchem.6c00231","url":null,"abstract":"Artificial oxygen carriers (AOCs) remain an unmet medical need in clinical practice. While hemoglobin is relatively safe within red blood cells, its release into circulation causes complications due to hemoglobin degradation forming toxic hemin. Here we report the design and synthesis of a novel heme–intrinsically disordered peptide (Heme–IDP) conjugate as a potential prototype for next-generation AOCs. Heme–IDP demonstrates markedly reduced cytotoxicity compared with free hemin and protoporphyrin IX (PPIX). Fluorescence imaging further indicates that negatively charged IDP significantly reduces PPIX cellular uptake, contributing to improved biocompatibility of Heme–IDP. The use of d-enantiomeric IDP sequences enhances peptide stability. Spectroscopic analyses confirm that Heme–IDP retains the ability for axial binding. These results highlight the potential of d-peptide-based IDP to mitigate the intrinsic toxicity associated with heme derivatives, offering a promising new direction for the development of safer and more biocompatible AOCs.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1341–1349"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.6c00231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349967","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