Bioconjugate Chemistry最新文献_第2页

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 : 2025-07-16 Epub 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":"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":"1448-1460"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","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

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-16

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

引用次数: 0

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-16

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

引用次数: 0

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-16

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

引用次数: 0

Cell Labeling with Responsive MRI Contrast Agents is Enabled through Solid-Phase Synthesis. 响应性MRI造影剂的细胞标记通过固相合成实现。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-16 Epub Date: 2025-05-07 DOI: 10.1021/acs.bioconjchem.5c00005

Liam Connah, Danijela Bataveljić, Aleksandra M Bondžić, Lucía Cabrera Fernández De Henestrosa, Andrej Korenić, Bojan P Bondžić, Pavle Andjus, Goran Angelovski

{"title":"Cell Labeling with Responsive MRI Contrast Agents is Enabled through Solid-Phase Synthesis.","authors":"Liam Connah, Danijela Bataveljić, Aleksandra M Bondžić, Lucía Cabrera Fernández De Henestrosa, Andrej Korenić, Bojan P Bondžić, Pavle Andjus, Goran Angelovski","doi":"10.1021/acs.bioconjchem.5c00005","DOIUrl":"10.1021/acs.bioconjchem.5c00005","url":null,"abstract":"Bioresponsive or smart contrast agents (SCAs) for magnetic resonance imaging (MRI) can facilitate functional molecular imaging of numerous biological processes. These are MRI probes that alter the MRI signal along with the concentration changes of different biomarkers in their microenvironment, thus enabling the assessment of tissue physiology with high spatiotemporal resolution. One of the common shortcomings of SCA is their structural and functional insufficiency for accumulation in the targeted region, i.e., most frequently internalization into the cells to study the intracellular processes. Here, we report a strategy to prepare a multifunctional SCA that can be successfully incorporated into the cell membrane and internalized. We used the solid-phase synthesis methodology to obtain a trimeric SCA responsive to calcium ions, which bears a hydrophobic tetradecanoyl group to facilitate interaction with primary rat astrocytes. The developed MRI probe maintained high activity, exhibiting high calcium-triggered longitudinal and transverse relaxivity changes. Concurrently, it showed the ability to label the cell membranes and internalize into the astroglial cells while not causing cytotoxicity or affecting the electrophysiology of the cells.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1384-1393"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951271","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

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 : 2025-07-16 Epub 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

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 : 2025-07-16 Epub 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":"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":"1438-1447"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","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

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 : 2025-07-16 Epub 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":"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":"1483-1493"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272539/pdf/","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":"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 : 2025-07-16

Ritam Das, Jewel Medeiros, Jithu Krishna, Sriya Munugoti, Ranit Dutta, Anirudh Devarajan, Arpan Ghosh and S. Thayumanavan*,

引用次数: 0

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-07-16

Elise Ishida, Richard Dambra, Sally Ye, Steven Anderlot, Andrea Matter, Kaitlynn Graca, Yoo-Chun Kim, Travis Whitney, Yuecheng Xi, Leila Eslamizar, Ting Wang, Tom S. Chan, Sadia Abid, Leela Kurien, Mary Sanville, Aishwarya Bapat, Theophila Dusabamahoro, Andrey Konovalov, Amy Mikolaichik, Miguel A. Miranda-Roman, Audrey Brenot, Charles Wood, Birgit Fogal, Aaron M. Teitelbaum, Kelly Coble, Michael Franti, Kerstin Schaefer, Joseph Ashour* and Hamid Samareh Afsari*,

引用次数: 0