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A Thermostable Fatty Acid Hydratase from Marinitoga Piezophila with Low Temperature Optimum and Broad Product Scope 一种低温最适产范围广的嗜热马里尼托加脂肪酸水合酶。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-26 DOI: 10.1002/cbic.202500081
Niels Krabbe Johnsen, David Marlo Werenberg Marcher, Mathias Bille Nielsen, Yan Zhang, Zheng Guo, Bekir Engin Eser
{"title":"A Thermostable Fatty Acid Hydratase from Marinitoga Piezophila with Low Temperature Optimum and Broad Product Scope","authors":"Niels Krabbe Johnsen,&nbsp;David Marlo Werenberg Marcher,&nbsp;Mathias Bille Nielsen,&nbsp;Yan Zhang,&nbsp;Zheng Guo,&nbsp;Bekir Engin Eser","doi":"10.1002/cbic.202500081","DOIUrl":"10.1002/cbic.202500081","url":null,"abstract":"<p>Hydroxy fatty acids (HFAs) are valuable derivatives of fatty acids (FAs) with interesting bioactivities. Moreover, they are used in materials industry as additives, starting materials and surfactants. HFAs can be produced from FAs either by hydroxylation or by hydration reaction, if FA is unsaturated, using chemical or enzymatic methods. FA hydratases (FAHs) are promising biocatalysts for HFA synthesis thanks to their non-redox nature, high efficiency and excellent selectivity. Although FAHs are relatively more stable compared to other enzymes like monooxygenases, their tolerance to high temperature and organic solvents is limited. In this study, we characterized a rare thermostable FAH ortholog through database gene mining. This enzyme from <i>Marinitoga Piezophila</i>, a thermo-piezophilic organism, displayed novel properties, including broad substrate scope, broad pH range, unique regioselectivity and excellent thermostability (retaining full activity after 30 min incubation at 70 °C); however, quite interestingly, its temperature optimum was at 20 °C. Although kinetic parameters indicate a less efficient enzyme compared to some other FAHs, the enzyme can reach over 90% conversion within 24 h at a 100 mL scale reaction containing 1.75 mM substrate. Furthermore, mutagenesis of key active-site residues indicated a possibly different reaction mechanism compared to earlier proposed mechanisms.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aspartimide Formation and Its Prevention in Fmoc Chemistry Solid Phase Peptide Synthesis Fmoc化学固相肽合成中阿斯巴胺的形成及其预防。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-26 DOI: 10.1002/cbic.202500490
Marco J. W. Kong, Tim J. H. P. van den Braak, Kevin Neumann
{"title":"Aspartimide Formation and Its Prevention in Fmoc Chemistry Solid Phase Peptide Synthesis","authors":"Marco J. W. Kong,&nbsp;Tim J. H. P. van den Braak,&nbsp;Kevin Neumann","doi":"10.1002/cbic.202500490","DOIUrl":"10.1002/cbic.202500490","url":null,"abstract":"<p>Aspartimide formation remains a persistent challenge during Fmoc chemistry solid phase peptide synthesis. This review outlines various strategies to suppress base-mediated aspartimide formation, including the use of ester β-carboxyl protecting groups, non-ester-based β-carboxyl masking groups, and backbone-protecting groups. In addition, alternatives to the Fmoc group are explored that are cleavable under nonbasic conditions. The work discussed in this review highlights that the continued development of compatible and scalable tactics toward aspartimide prevention is essential for advancing peptide synthesis in both research and industry.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Front Cover: Chromenone Derivatives as CRM1 Inhibitors for Targeting Glioblastoma (ChemBioChem 15/2025) 封面:染色质衍生物作为靶向胶质母细胞瘤的CRM1抑制剂(ChemBioChem 15/2025)
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-25 DOI: 10.1002/cbic.70013
Salvatore Princiotto, Lucía Jiménez, Lucía Domínguez, João G. N. Sequeira, Cristiana Mourato, Alba Orea-Soufi, Bruno Santos, Sabrina Dallavalle, Miguel Machuqueiro, Bibiana I. Ferreira, Wolfgang Link
{"title":"Front Cover: Chromenone Derivatives as CRM1 Inhibitors for Targeting Glioblastoma (ChemBioChem 15/2025)","authors":"Salvatore Princiotto,&nbsp;Lucía Jiménez,&nbsp;Lucía Domínguez,&nbsp;João G. N. Sequeira,&nbsp;Cristiana Mourato,&nbsp;Alba Orea-Soufi,&nbsp;Bruno Santos,&nbsp;Sabrina Dallavalle,&nbsp;Miguel Machuqueiro,&nbsp;Bibiana I. Ferreira,&nbsp;Wolfgang Link","doi":"10.1002/cbic.70013","DOIUrl":"10.1002/cbic.70013","url":null,"abstract":"<p>The cover image illustrates the inhibition of the nuclear export receptor CRM1 by a small molecule inhibitor (in red) that covalently binds to cysteine at position 528. CRM1, a ring-shaped protein, is overexpressed in several human cancers, including glioblastoma (GBM). Its inhibition can disrupt three key oncogenic signaling pathways that drive GBM progression. CRM1 facilitates the nuclear export of proteins containing a nuclear export signal through the nuclear pore complex (depicted in yellow), which is embedded in the nuclear envelope, from the nucleus to the cytoplasm. More details can be found in the article 10.1002/cbic.202500195 by Wolfgang Link and co-workers.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 15","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cover Feature: Characterization of the Cubamyces Menziesii Terpenome (ChemBioChem 15/2025) 封面专题:Cubamyces Menziesii Terpenome的表征(ChemBioChem 15/2025)
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-25 DOI: 10.1002/cbic.70014
Létitia Leydet, Julie Couillaud, Agnès Amouric, Elise Courvoisier-Dezord, Carole Avesque, Thierry Giardina, Mireille Attolini, Pierre Rousselot-Pailley, Katia Duquesne, Marie-Noelle Rosso, Gilles Iacazio
{"title":"Cover Feature: Characterization of the Cubamyces Menziesii Terpenome (ChemBioChem 15/2025)","authors":"Létitia Leydet,&nbsp;Julie Couillaud,&nbsp;Agnès Amouric,&nbsp;Elise Courvoisier-Dezord,&nbsp;Carole Avesque,&nbsp;Thierry Giardina,&nbsp;Mireille Attolini,&nbsp;Pierre Rousselot-Pailley,&nbsp;Katia Duquesne,&nbsp;Marie-Noelle Rosso,&nbsp;Gilles Iacazio","doi":"10.1002/cbic.70014","DOIUrl":"10.1002/cbic.70014","url":null,"abstract":"<p>The cover illustrates the vast diversity of sesquiterpenes produced by the fungus <i>Cubamyces menziesii</i>. A bioinformatics analysis revealed that this polyploid organism carries a surprisingly high number of genes encoding sesquiterpene cyclases. Using an in vitro approach, the authors aim to decipher the terpenome of this fungus and explore the wide range of applications of these compounds in fields such as the flavor industry, food, and medicine. More information can be found in the article 10.1002/cbic.202401083 by Katia Duquesne, Marie-Noelle Rosso, Gilles Iacazio, and co-workers.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 15","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Light-Triggered Disassembly of Peptide Nanostructures 肽纳米结构的光触发分解。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-14 DOI: 10.1002/cbic.202500414
Raphael Meyer, Julian Link, Lucas Gunkel, Albin Lahu, Hakan Demirezen, Tanja Weil, David Y. W. Ng
{"title":"Light-Triggered Disassembly of Peptide Nanostructures","authors":"Raphael Meyer,&nbsp;Julian Link,&nbsp;Lucas Gunkel,&nbsp;Albin Lahu,&nbsp;Hakan Demirezen,&nbsp;Tanja Weil,&nbsp;David Y. W. Ng","doi":"10.1002/cbic.202500414","DOIUrl":"10.1002/cbic.202500414","url":null,"abstract":"<p>While the assembly of supramolecular peptide nanostructures with diverse functions and morphologies has been extensively studied, the controlled disassembly of these architectures remains less understood. To address this, two short amphiphilic peptides incorporating anthracene as a light-responsive unit and lysine as a pH-sensitive residue are designed. These peptides self-assemble into nanosheets or nanoribbons with distinct secondary structures, which are further tunable by pH through modulation of peptide charge. Upon irradiation at 365 nm, the anthracene moieties undergo a bimolecular [4 + 4] cycloaddition, disrupting the π–π stacking interactions by distorting the planarity of the aromatic units. This photoreaction leads to disassembly of the supramolecular architectures within 10 min. Unlike monomolecular reactions such as photocleavage, the kinetics of this bimolecular photodimerization are significantly influenced by the degree of preorganization within the assemblies. These findings underscore the critical interplay between supramolecular architecture and molecular photochemistry, enabling light-triggered, structure-dependent disassembly of diverse peptide nanostructures.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthesis of Oligonucleotides Containing a Dna Distorting Interstrand Crosslink Produced by Mitomycins 丝裂霉素产生的含有Dna扭曲链交联的寡核苷酸的合成。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-14 DOI: 10.1002/cbic.202500221
Sarah Marks, Gabriel Martinez, Michael Adamov, Christopher Alley, Bianca Davila, Ana G. Petrovic, Rinat Abzalimov, Padmanava Pradhan, Marta Concheiro-Guisan, Elise Champeil
{"title":"Synthesis of Oligonucleotides Containing a Dna Distorting Interstrand Crosslink Produced by Mitomycins","authors":"Sarah Marks,&nbsp;Gabriel Martinez,&nbsp;Michael Adamov,&nbsp;Christopher Alley,&nbsp;Bianca Davila,&nbsp;Ana G. Petrovic,&nbsp;Rinat Abzalimov,&nbsp;Padmanava Pradhan,&nbsp;Marta Concheiro-Guisan,&nbsp;Elise Champeil","doi":"10.1002/cbic.202500221","DOIUrl":"10.1002/cbic.202500221","url":null,"abstract":"<p>Mitomycin C (MC) is a powerful chemotherapy agent currently used in clinics for the treatment of various types of cancer. MC functions by inhibiting cellular growth through the formation of cytotoxic interstrand crosslinks (ICLs). These ICLs induced by MC have minimal impact on the DNA backbone, preserving its B-DNA structure. Recent research suggests that the cellular machinery recognizes and repairs ICLs differently based on their specific structure. To better understand how DNA distortion caused by MC ICLs influences cytotoxic effects, Herein, a novel mitomycin ICL is synthiesized that, unlike MC, significantly distorts DNA and widens the minor groove. This work outlines the synthesis of oligonucleotides bearing a single monoadduct or a single ICL of this new MC derivative at a defined position. Such substrates are widely used for investigations into biological processes such as DNA damage/repair studies. The monoadducted and crosslinked oligonucleotides are thoroughly characterized using various techniques, including enzymatic digestion to nucleosides, mass and circular dichroism spectroscopy, as well as thermal denaturation studies. Furthermore, the structure of this novel crosslinked duplex is compared with that of less-distorting mitomycin ICLs using Molecular Dynamics simulations.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Applications of Fluidized Bed Reactors in Biocatalysis 流化床反应器在生物催化中的应用。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-14 DOI: 10.1002/cbic.202500143
Nadia Guajardo, Paula Grez, Ricardo S. Schrebler, Rodrigo A. Schrebler
{"title":"Applications of Fluidized Bed Reactors in Biocatalysis","authors":"Nadia Guajardo,&nbsp;Paula Grez,&nbsp;Ricardo S. Schrebler,&nbsp;Rodrigo A. Schrebler","doi":"10.1002/cbic.202500143","DOIUrl":"10.1002/cbic.202500143","url":null,"abstract":"<p>The main objective of this article is to review previous contributions on the applications of fluidized bed reactors (FBR) in biocatalysis. FBR combines the properties of a stirred tank reactor and a continuous tubular reactor, making it an efficient system for carrying out enzymatic reactions with immobilized enzymes. This equipment's advantages include its high transfer capacity and versatility, as it can be used with liquid and gaseous phases. According to the literature, these devices have been primarily used to degrade contaminants, synthesize cosmetic ingredients, produce food and pharmaceutical compounds, and synthesize biolubricants and biodiesel. The enzymes most used in fluidized bed mode are laccases, lipases, and proteases immobilized on methacrylate resins, mesoporous silicas, alginate, and chitosan beads. Enzyme immobilization is essential, as it can promote the suspension of biocatalyst particles, thereby increasing yields and productivity. One of the leading prospects for these systems is to stabilize the fluidized bed using a magnetic field and the concept of “microfluidization,” which enables the stabilization of smaller biocatalyst particles with smaller equipment, thereby increasing efficiency and intensifying the biocatalytic process. In the future, the versatility of FBR will constitute an attractive alternative for developing biocatalytic systems.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering Proteinosomes with Cellular-Like Functionalities 具有细胞样功能的工程蛋白体。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-14 DOI: 10.1002/cbic.202500448
Renzhuo Li, Xiaoman Liu, Xin Huang
{"title":"Engineering Proteinosomes with Cellular-Like Functionalities","authors":"Renzhuo Li,&nbsp;Xiaoman Liu,&nbsp;Xin Huang","doi":"10.1002/cbic.202500448","DOIUrl":"10.1002/cbic.202500448","url":null,"abstract":"<p>Recent development of various types of functional microcompartmentalized ensembles that can imitate rudimentary aspects of living cells has attracted great attentions in a wide range of research communities. Proteinosome is one typical form of these biomimetic structures. Significant advances in their construction have indicated that by utilizing interfacial self-assembly, polymer-based membrane templating, and hybrid lipid–polymer systems can achieve tunable permeability, mechanical stability, and stimuli–responsive behaviors, which is detailedly elaborated in this review. Additionally, this review emphasizes their functionalization strategies that enable programable bioactivity and communication, as well as community aggregation structures to build prototissues exhibiting cellular-like behaviors. Innovations in stimuli–responsive materials and multicompartmentalized architectures further enhance spatiotemporal control over biochemical processes, while the convergence of polymer chemistry, synthetic biology, and nanotechnology continues to expand the functional scope of proteinosomes, positioning them as transformative tools for next-generation artificial cell models or biomimetic materials. Having covered these topics in depth, this review hopes to inspire additional investigation into the research methodologies related to proteinosomes, furthermore the artificial cells, as well as possible applications in targeted cancer therapy, gene therapy, and artificial organelles design.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diastereoselective, Diversifiable Synthesis and Biological Evaluation of the Virginiamycin Inducers, the Virginiae Butanolides 维吉尼亚霉素诱导剂维吉尼亚丁内酯的非对映选择性、多样化合成及生物学评价。
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-14 DOI: 10.1002/cbic.202500386
Kylie G. Castator, Manuela Frias-Gomez, Lauren E. Wilbanks, Elizabeth I. Parkinson
{"title":"Diastereoselective, Diversifiable Synthesis and Biological Evaluation of the Virginiamycin Inducers, the Virginiae Butanolides","authors":"Kylie G. Castator,&nbsp;Manuela Frias-Gomez,&nbsp;Lauren E. Wilbanks,&nbsp;Elizabeth I. Parkinson","doi":"10.1002/cbic.202500386","DOIUrl":"10.1002/cbic.202500386","url":null,"abstract":"<p><i>Streptomyces</i> species are renowned for their ability to produce bioactive natural products (NPs) via biosynthetic gene clusters (BGCs). However, many BGCs remain transcriptionally silent under standard laboratory conditions. Among the key regulatory mechanisms for NP biosynthesis are the <i>γ</i>-butyrolactone (GBL) signaling molecules, which have been widely studied for their role in repressor-molecule circuits. While the <i>S. coelicolor</i> butanolides (SCBs) and A-factor from <i>S. griseus</i> have been extensively studied, the virginiae butanolides (VBs) from <i>S. virginiae,</i> which alleviate repression of the biosynthesis of the antibiotic virginiamycins via binding to the cluster situated TetR-like repressor BarA, remain understudied. This is in large part due to limited access to enantiopure VBs. Herein, we report a diastereoselective and diversifiable route to access the VB hormones, starting from a protected (<i>R</i>)-paraconyl alcohol intermediate. A library of VB derivatives was synthesized and tested for their ability to alleviate repression of BarA using a newly developed green fluorescent protein (GFP) reporter assay. The synthesis and assay described herein established the most quantitative structure–activity relationship (SAR) analysis of the VBs to date. Overall, this study provides new tools for probing NP regulation in <i>Streptomyces</i> and enables new strategies for BGC activation using synthetic GBL molecules.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual-Targeting of PD-L1 and Integrin αvβ3 for Preclinical PET Imaging of Cancer PD-L1和整合素αvβ3在肿瘤临床前PET成像中的双重靶向作用
IF 2.8 4区 生物学
ChemBioChem Pub Date : 2025-08-14 DOI: 10.1002/cbic.202500508
Wenhao Liu, Xiushuang Yuan, Siqi Zhang, Xingkai Wang, Xin Gao, Hao Tian, Dun Wang, Ming-Rong Zhang, Rui Wang, Kuan Hu
{"title":"Dual-Targeting of PD-L1 and Integrin αvβ3 for Preclinical PET Imaging of Cancer","authors":"Wenhao Liu,&nbsp;Xiushuang Yuan,&nbsp;Siqi Zhang,&nbsp;Xingkai Wang,&nbsp;Xin Gao,&nbsp;Hao Tian,&nbsp;Dun Wang,&nbsp;Ming-Rong Zhang,&nbsp;Rui Wang,&nbsp;Kuan Hu","doi":"10.1002/cbic.202500508","DOIUrl":"10.1002/cbic.202500508","url":null,"abstract":"<p>The dual-targeting strategy has demonstrated advantages in enhancing tumor uptake, improving imaging contrast, and ultimately increasing tumor detection rate. PD-L1 is overexpressed on multiple tumor cells and regulated by <i>α</i><sub>v</sub><i>β</i><sub>3</sub>-integrin. In this study, a dual-targeting radiotracer, [64Cu]-PEG-RGD-TPP-1, is developedfor PET/CT imaging of both PD-L1 and <i>α</i><sub>v</sub><i>β</i><sub>3</sub>-integrin simultaneously, achieving high contrast, enhanced tumor uptake, and prolonged tumor retention time. [<sup>64</sup>Cu]-PEG-RGD-TPP-1 comprises the peptide TPP-1 and cyclic peptide c(RGDyC), linked via a PEG linker. The dual-targeting molecule had a moderate serum stability (≈60%) in vivo after 1 hr. This dual-targeting radiotracer is evaluated and compared with the single-targeting radiotracers [<sup>64</sup>Cu]-PEG-TPP-1 and [<sup>64</sup>Cu]-TPP-1. PET imaging and <i>ex vivo</i> biodistribution studies show that [<sup>64</sup>Cu]-PEG-RGD-TPP-1 exhibits higher tumor uptake than its single-targeting counterparts. Moreover, the dual-targeting radiotracer demonstrated potential for ultrasmall tumor imaging and could be combined with X-ray irradiation to further enhance PET imaging contrast, thereby improving tumor-targeting efficiency. These findings suggest that [<sup>64</sup>Cu]-PEG-RGD-TPP-1 is a promising noninvasive tracer for detecting tumors expressing PD-L1 and/or integrin <i>a</i><sub>v</sub><i>β</i><sub>3</sub>, with the prospect of clinical implementation.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","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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