Bioconjugate Chemistry最新文献

Addition of Oligoarginine to a Membrane Permeabilizing Peptide M-Lycotoxin Facilitates Intracellular Antibody Infusion from Microcondensate. 在膜渗透肽m -番茄毒素中添加低精氨酸有助于微凝析液中细胞内抗体的输注。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-02 DOI: 10.1021/acs.bioconjchem.5c00176

Junya Michibata, Yoshimasa Kawaguchi, Yusei Furuyama, Yoshihiro Sasaki, Kazunari Akiyoshi, Shiroh Futaki

{"title":"Addition of Oligoarginine to a Membrane Permeabilizing Peptide M-Lycotoxin Facilitates Intracellular Antibody Infusion from Microcondensate.","authors":"Junya Michibata, Yoshimasa Kawaguchi, Yusei Furuyama, Yoshihiro Sasaki, Kazunari Akiyoshi, Shiroh Futaki","doi":"10.1021/acs.bioconjchem.5c00176","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00176","url":null,"abstract":"Coacervate-based intracellular delivery of biomacromolecules has attracted our attention due to the feasibility of easy condensation of the biomacromolecules and their controllable release. Our laboratory has developed a unique, coacervate-based delivery system that uses the conjugate of the polysaccharide pullulan with membrane-permeabilizing peptides, including L17E and M-lycotoxin. This system enables immunoglobulin G (IgG) antibodies labeled with the negatively charged fluorophore Alexa Fluor 488 to enter the cytosol directly through the plasma membrane. Cyotosolic IgG distribution is complete within a few minutes after infusion initiation, and infusion can be achieved in serum-containing medium. The purpose of this study was to refine this system to reduce the amount of antibody required while maintaining satisfactory delivery efficiencies. Therefore, pullulan conjugates with M-lytocoxin bearing two to eight arginine residues were designed to enhance the interaction of M-lycotoxin with the cell membrane. The conjugates were able to form microcondensates with Alexa Fluor 488 labeled IgGs. The addition of arginine residues improved the efficiency of cytosolic infusion and successfully reduced the amounts of both antibodies and pullulan-peptide conjugates required for the delivery.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537396","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

Modulation of Membrane-Disruptive Activity of Melittin via N- and C-Terminal PEGylation Strategies. 通过N端和c端聚乙二醇化策略调节蜂毒素的膜破坏活性。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-01 DOI: 10.1021/acs.bioconjchem.5c00123

Haonan Chen, Yuhang Dong, Feng Shi, Feng Li

{"title":"Modulation of Membrane-Disruptive Activity of Melittin via N- and C-Terminal PEGylation Strategies.","authors":"Haonan Chen, Yuhang Dong, Feng Shi, Feng Li","doi":"10.1021/acs.bioconjchem.5c00123","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00123","url":null,"abstract":"Melittin has emerged as a promising therapeutic agent due to its potent antitumor and antimicrobial activities. However, the clinical translation of native Melittin is hindered by substantial challenges, including systemic toxicity and rapid proteolytic degradation, leading to suboptimal pharmacokinetic profiles. Therefore, structure-activity relationship-guided rational design strategies focusing on the molecular determinants of membrane penetration mechanisms are essential for optimizing Melittin's therapeutic index. Herein, we synthesized a series of Melittin derivatives with varying PEG modification lengths and N- or C-terminus. Our evaluation revealed that N-terminal PEGylation substantially mitigated the cytotoxicity and hemolytic activity of Melittin while enhancing its proteolytic stability, where these beneficial properties exhibited progressive enhancement correlating with increasing PEG chain length. Conversely, C-terminal PEGylation demonstrated limited efficacy in modulating Melittin's toxicity profile. Our findings elucidated that the membrane interaction mechanism of Melittin was predominantly mediated by its N-terminal helical domain, rather than the C-terminus, which initiated the cell membrane binding and subsequent pore formation, ultimately culminating in cell demise. This finding underscored the critical role of the N-terminus in the biological activity of Melittin. This study provided insight into the structure-activity relationship of PEGylated Melittin and established guidance for creating the next generation of peptide therapies.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537397","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

Fluorescent PSMA-Targeted Radiotheranostic Compounds for Multiscale Imaging. 用于多尺度成像的荧光psma靶向放射治疗化合物。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-27 DOI: 10.1021/acs.bioconjchem.5c00139

G G Simpson, J M Quintana, J E Carrothers, F Jiang, S A Walker, C Cho, R Weissleder, M A Miller, T S C Ng

{"title":"Fluorescent PSMA-Targeted Radiotheranostic Compounds for Multiscale Imaging.","authors":"G G Simpson, J M Quintana, J E Carrothers, F Jiang, S A Walker, C Cho, R Weissleder, M A Miller, T S C Ng","doi":"10.1021/acs.bioconjchem.5c00139","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00139","url":null,"abstract":"Prostate-specific membrane antigen (PSMA) is a promising theranostic target. Different PSMA-targeting small molecule ligands have been FDA-approved or are in development, yet their biological fate at the single-cell level is often unknown. An improved understanding of the cellular distribution of these probes will confer insights into their microdosimetry and guide next-generation theranostic probe development. To enable detailed single-cell pharmacokinetics, it is desirable to have fluorescence affinity ligands that preserve the properties of the native agent. Building upon the structure of the FDA-approved PSMA-617, we synthesized a panel of fluorescent analogs and evaluated their in vitro and in vivo properties. We described a facile solid-phase-based synthesis and optimized the synthesis of the crucial urea pharmacophore. We identified two compounds, PSMA-Lys-DOTA-Cy680 (3) and PSMA-Lys-DOTA-AF647 (4), with similar PSMA binding affinities compared to the parent compound and robust optical imaging properties. Tissue and cellular biodistribution data from imaging can populate microdosimetric and systemic modeling to provide potential insights into future radiopharmaceutical therapy design.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504141","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

Impact of Conjugation Chemistry on the Pharmacokinetics of Peptide-Polymer Conjugates in a Model of Traumatic Brain Injury. 偶联化学对外伤性脑损伤模型中肽-聚合物偶联物药代动力学的影响。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-27 DOI: 10.1021/acs.bioconjchem.5c00175

Jason Ren Wu, Akash Canjels, Rei Miyauchi, Ester J Kwon

{"title":"Impact of Conjugation Chemistry on the Pharmacokinetics of Peptide-Polymer Conjugates in a Model of Traumatic Brain Injury.","authors":"Jason Ren Wu, Akash Canjels, Rei Miyauchi, Ester J Kwon","doi":"10.1021/acs.bioconjchem.5c00175","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00175","url":null,"abstract":"Traumatic brain injury (TBI) remains a leading cause of long-term disability and mortality; however, there are no effective therapies to mitigate secondary injury and long-term neurological impairments. After the initial mechanical insult, there is a secondary injury that leads to neuroinflammation and blood-brain barrier (BBB) disruption, both of which are linked to changes in the extracellular matrix (ECM). A short peptide sequence, CAQK (Cys-Ala-Gln-Lys), targets upregulated ECM proteoglycans after TBI and has exhibited therapeutic properties in preclinical TBI studies. However, like many peptides, CAQK has poor pharmacokinetics, with rapid systemic clearance limiting its therapeutic potential. To overcome these limitations, we investigated a peptide-polymer conjugate using a poly(ethylene glycol) (PEG) scaffold to improve the peptide pharmacokinetics of CAQK. We synthesized materials using two conjugation chemistries, maleimide-thiol Michael-type addition and dibenzocyclooctyne (DBCO)-azide strain-promoted azide-alkyne cycloaddition. The impact of linker selection on biodistribution and clearance was distinct. We first showed that conjugation of CAQK to PEG, irrespective of linkers, significantly extended the peptide's blood half-life by 90-fold and increased brain accumulation. In the analysis of off-target organs, we observed longer retention of DBCO conjugates in the liver, kidney, and spleen compared to maleimide conjugates. Given the high incidence of TBI in populations such as military personnel and athletes, we explored whether our long-circulating material could be given as a prophylaxis. We demonstrated the accumulation of 4.5%ID/g CAQK in the injured brain when the conjugate was delivered prophylactically 24 h before injury. Our work underscores the advantage of long-circulating peptide-polymer conjugates in the context of TBI and the impact of conjugation chemistry on pharmacokinetics.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511263","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

Near Infrared Light-Triggered Small Molecule Chemical Reactions in Biocompatible Systems. 生物相容性系统中近红外光触发的小分子化学反应。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-27 DOI: 10.1021/acs.bioconjchem.5c00293

Jie Zhong, Yuhang Li, Xiaotong Li, Feng Liang, Ran Tao, Shan Qian, Xinyuan Fan

{"title":"Near Infrared Light-Triggered Small Molecule Chemical Reactions in Biocompatible Systems.","authors":"Jie Zhong, Yuhang Li, Xiaotong Li, Feng Liang, Ran Tao, Shan Qian, Xinyuan Fan","doi":"10.1021/acs.bioconjchem.5c00293","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00293","url":null,"abstract":"Near-infrared (NIR) light, within the 700-1000 nm therapeutic optical window, offers deep tissue penetration, low photocytotoxicity, and minimal side effects, making it ideal for remote control of biocompatible reactions in vivo. This review explores recent advances in NIR-triggered reactions, focusing on direct and indirect activation strategies. Direct approaches utilize NIR-responsive protecting groups, while indirect methods employ upconversion materials and photocatalysis to overcome NIR's energy limitations. These innovations expand noninvasive in vivo control capabilities. Applications include NIR-mediated drug delivery, biological molecule activation, and proximity labeling for protein interaction studies. Such reactions enable precise modulation of biological events under native conditions. The review highlights the potential of integrating advanced nanomaterials and optimizing indirect activation techniques to enhance reaction efficiency. It also emphasizes the requirement for interdisciplinary collaboration to refine NIR-responsive systems and facilitate clinical translation. By showcasing state-of-the-art NIR-controlled chemistry and identifying key areas for future research, this work aims to inspire advancements in biomedical research and therapeutics. Addressing the challenges of in vivo chemical control, this review positions NIR chemistry as a critical component in the evolution of biocompatible reaction methodologies.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504142","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

Chemo-Enzymatic Synthesis of Viscoelastic Pseudopeptidoglycan Networks. 粘弹性假多肽聚糖网络的化学酶合成。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-24 DOI: 10.1021/acs.bioconjchem.5c00014

Philipp Loibner, David Bučak-Gasser, Katharina Schober, Tobias Steindorfer, Monika Brandtner, Tobias Dorn, Tanja Wrodnigg, Dmytro Neshchadin, Georg Gescheidt-Demner, Matej Bračič, Florian Lackner, Tamilselvan Mohan, Karin Stana Kleinschek, Rupert Kargl

引用次数: 0

A Mild Protecting-Group Free Strategy for Neoglycoconjugate Synthesis. 新糖缀合物的温和无保护基团合成策略。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-23 DOI: 10.1021/acs.bioconjchem.5c00138

Princey Raju, Chunhua Dong, Craig R Garen, Michael T Woodside, Christopher W Cairo

{"title":"A Mild Protecting-Group Free Strategy for Neoglycoconjugate Synthesis.","authors":"Princey Raju, Chunhua Dong, Craig R Garen, Michael T Woodside, Christopher W Cairo","doi":"10.1021/acs.bioconjchem.5c00138","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00138","url":null,"abstract":"The synthesis of neoglycoconjugates has paved the way for the discovery of novel probes that mimic natural glycoconjugates and can provide designed research tools and therapeutics. In some cases, the target protein may not be amenable to harsh conditions; therefore, semisynthetic or chemical methods must be chosen with care. Here, we present a simple and modular chemoselective coupling strategy between an unprotected sugar and an N,O-disubstituted hydroxylamine under mild acidic conditions. This strategy removes any need for protecting groups on the glycan. The terminal alkene group of the conjugate serves as an effective handle to allow facile conjugation to the protein of interest via thiol-ene coupling (TEC), with proteins bearing a cysteine or free thiol to prepare neoglycoconjugates. We demonstrate that the strategy is compatible with both N- and O-linked glycans using protecting-group free strategies and optimize the TEC conditions using a variety of photocatalysts. Finally, we test the method on an aggregation-prone protein, α-synuclein. We envision that this strategy could allow the construction of complex glycoconjugates for biological testing using isolated glycans, or for generation of conjugates where the protein of interest is sensitive to harsh conditions.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473407","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

TfR1-Binding Peptide Conjugation Facilitates Robust and Specific siRNA Delivery to the Central Nervous System. tfr1结合肽偶联促进强大和特异性siRNA传递到中枢神经系统。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-21 DOI: 10.1021/acs.bioconjchem.5c00225

Tiancheng Fu, Fushun Fan, Yingying Lin, Zhenxian Mo, Minhua Zhou, Xiaolan Ye, Xiong Cai, Zaijun Zhang, Changgeng Qian, Xinjian Liu

引用次数: 0

Design and Evaluation of Stable Cysteine-Modified Monobody Scaffolds for Mirror-Image Synthesis. 稳定半胱氨酸修饰单体镜像合成支架的设计与评价。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-21 DOI: 10.1021/acs.bioconjchem.5c00181

Naoya Iwamoto, Saya Ohno, Kensuke Nakamura, Toshinori Naito, Sayaka Miura, Shinsuke Inuki, Hiroaki Ohno, Gosuke Hayashi, Hiroshi Murakami, Shinya Oishi

引用次数: 0

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-06-18

Quentin Vicentini, Dennis Hekman, Deepak Bhatt, Rouven Stulz, Mahya Dezfouli, Peter Gennemark, Nicola Guzzi, Naoko Toki, Bojana Lazovic, Carolina Tängemo, Shalini Andersson, Samir EL Andaloussi* and Anders Dahlén*,

引用次数: 0