Bioconjugate Chemistry最新文献

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Self-Assembly of Toll-Like Receptor (TLR2/6) Agonist Lipidated Amino Acid or Peptide Conjugates: Distinct Morphologies and Bioactivities.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-04-02 DOI: 10.1021/acs.bioconjchem.5c00051
Valeria Castelletto, Lucas R de Mello, Juliane Pelin, Ian W Hamley
{"title":"Self-Assembly of Toll-Like Receptor (TLR2/6) Agonist Lipidated Amino Acid or Peptide Conjugates: Distinct Morphologies and Bioactivities.","authors":"Valeria Castelletto, Lucas R de Mello, Juliane Pelin, Ian W Hamley","doi":"10.1021/acs.bioconjchem.5c00051","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00051","url":null,"abstract":"<p><p>Toll-like receptor (TLR) agonists are of interest in immunotherapy and cancer vaccines. The most common agonists of TLR2 are based on Pam<sub>2</sub>Cys or Pam<sub>3</sub>Cys. In the former, two palmitoyl (Pam) fatty acids are linked to a glycerylcysteine motif by ester linkages. Pam<sub>3</sub>Cys is analogous but contains an extra Pam group on the α-amine. Here, we compare the self-assembly in aqueous solution of the parent Pam<sub>2</sub>CysOH and Pam<sub>3</sub>Cys amino acid conjugates to that of Pam<sub>2</sub>CysSK<sub>4</sub> and Pam<sub>3</sub>CysSK<sub>4</sub> which are potent TLR2 agonists bearing the CysSK<sub>4</sub> peptide sequence. All four conjugates exhibit a critical aggregation concentration above which self-assembled structures are formed. We find through a combination of small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and confocal fluorescence microscopy remarkable differences in self-assembled nanostructures. Pam<sub>2</sub>CysOH and Pam<sub>3</sub>CysOH both form unilamellar vesicles, although these are larger for the latter compound, an effect ascribed to enhanced membrane rigidity. This is in contrast to previously reported morphologies for Pam<sub>2</sub>CysSK<sub>4</sub> and Pam<sub>3</sub>CysSK4, which are spherical micelles or predominantly wormlike micelles, respectively [Hamley, I. W.; et al. <i>Toll-like Receptor Agonist Lipopeptides Self-Assemble into Distinct Nanostructures</i>. Chem. Comm. 2014, 50, 15948-15951]. We also examine the effect of introduction in the bulky <i>N</i>-terminal Fmoc [fluorenylmethoxycarbonyl] group on the self-assembly of Fmoc-Pam<sub>2</sub>CysOH. This compound also forms vesicles (above a critical aggregation concentration, determined from dye probe fluorescence experiments) in aqueous solution, larger than those for Pam<sub>2</sub>CysOH and with a population of perforated/compound vesicles. The carboxyl-coated (and amino-coated for Pam<sub>2</sub>CysOH) vesicles demonstrated here represent a promising system for future development toward bionanotechnology applications such as immune therapies. Conjugates Pam<sub>2</sub>CysOH, Pam<sub>2</sub>CysSK<sub>4</sub>, and Pam<sub>3</sub>CysSK<sub>4</sub> show good cytocompatibility at low concentrations, and in fact, the cell compatibility extends over a wider concentration range for Pam<sub>2</sub>CysOH. The TLR2/6 agonist activity was assessed using an assay that probes secreted alkaline phosphatase (SEAP) in NF-κB-SEAP reporter HEK293 cells expressing human TLR2 and TLR6, and Pam<sub>2</sub>CySOH shows significant activity, although not to the extent of Pam<sub>2</sub>CysSK4 or Pam<sub>3</sub>CysSK<sub>4</sub>. Thus, Pam<sub>2</sub>CysOH in particular is of interest as a vesicle-forming TLR2/6 agonist and stimulator of immune response.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762484","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
Choice of an Optimal Modular Strategy for the Synthesis of DOTA-Containing Heterobivalent Agents Targeting PSMA and GRPr
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-04-02 DOI: 10.1021/acs.bioconjchem.5c0003310.1021/acs.bioconjchem.5c00033
Stanislav A. Petrov*, Gleb P. Grigoriev, Grigory A. Orlov, Nikolay Y. Zyk, Yuri K. Grishin, Vitaly A. Roznyatovsky, Maria A. Beloglazkina, Juliana V. Petrova, Aleksei E. Machulkin, Mariia S. Larkina, Anastasia Prach, Ruslan Varvashenya, Vitalina Bodenko, Evgenii Plotnikov, Mekhman S. Yusubov and Elena K. Beloglazkina, 
{"title":"Choice of an Optimal Modular Strategy for the Synthesis of DOTA-Containing Heterobivalent Agents Targeting PSMA and GRPr","authors":"Stanislav A. Petrov*,&nbsp;Gleb P. Grigoriev,&nbsp;Grigory A. Orlov,&nbsp;Nikolay Y. Zyk,&nbsp;Yuri K. Grishin,&nbsp;Vitaly A. Roznyatovsky,&nbsp;Maria A. Beloglazkina,&nbsp;Juliana V. Petrova,&nbsp;Aleksei E. Machulkin,&nbsp;Mariia S. Larkina,&nbsp;Anastasia Prach,&nbsp;Ruslan Varvashenya,&nbsp;Vitalina Bodenko,&nbsp;Evgenii Plotnikov,&nbsp;Mekhman S. Yusubov and Elena K. Beloglazkina,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0003310.1021/acs.bioconjchem.5c00033","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00033https://doi.org/10.1021/acs.bioconjchem.5c00033","url":null,"abstract":"<p >Heterodimeric approaches have emerged as a promising method for simultaneously targeting multiple receptors on tumor cells using a single molecule. Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) holds the potential to improve the accuracy of prostate cancer diagnosis. The aim of this study was to develop a convenient and simple modular strategy for the creation of heterobivalent (HBV) conjugates targeting PSMA/GRPr receptors. For this purpose, we developed and compared six alternative routes for the stereoselective synthesis of HBV conjugates designed to deliver the chelating agent DOTA to PSMA/GRPr receptors. The comparison of these alternative synthetic pathways took into account such factors as efficiency, complexity, synthesis, and purification details, as well as yields of the target compounds. Optimal conditions for the stereoselective synthesis of HBV ligands to PSMA and GRPr, which could serve as molecular platforms for the targeted delivery of therapeutic or diagnostic agents to these receptors, were revealed. For synthesized HBV ligand <b>26</b><sup><b>x</b></sup> and its HBV conjugate with DOTA <b>27</b>, the complete signal assignment in <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N NMR spectra was achieved using 2D NMR techniques. Based on these data, comprehensive signal assignments were provided for all final compounds in their NMR spectra. The final HBV conjugate <b>27</b> was labeled with Lu-177, with yields &gt;99%, and the obtained radiotracer was studied in vitro for its binding specificity, with determining of the <i>K</i><sub>D</sub> and <i>B</i><sub>max</sub> using LNCaP (PSMA+) and PC-3 (GRPr+) cell lines.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 4","pages":"748–761 748–761"},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832732","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
Choice of an Optimal Modular Strategy for the Synthesis of DOTA-Containing Heterobivalent Agents Targeting PSMA and GRPr.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-04-02 DOI: 10.1021/acs.bioconjchem.5c00033
Stanislav A Petrov, Gleb P Grigoriev, Grigory A Orlov, Nikolay Y Zyk, Yuri K Grishin, Vitaly A Roznyatovsky, Maria A Beloglazkina, Juliana V Petrova, Aleksei E Machulkin, Mariia S Larkina, Anastasia Prach, Ruslan Varvashenya, Vitalina Bodenko, Evgenii Plotnikov, Mekhman S Yusubov, Elena K Beloglazkina
{"title":"Choice of an Optimal Modular Strategy for the Synthesis of DOTA-Containing Heterobivalent Agents Targeting PSMA and GRPr.","authors":"Stanislav A Petrov, Gleb P Grigoriev, Grigory A Orlov, Nikolay Y Zyk, Yuri K Grishin, Vitaly A Roznyatovsky, Maria A Beloglazkina, Juliana V Petrova, Aleksei E Machulkin, Mariia S Larkina, Anastasia Prach, Ruslan Varvashenya, Vitalina Bodenko, Evgenii Plotnikov, Mekhman S Yusubov, Elena K Beloglazkina","doi":"10.1021/acs.bioconjchem.5c00033","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00033","url":null,"abstract":"<p><p>Heterodimeric approaches have emerged as a promising method for simultaneously targeting multiple receptors on tumor cells using a single molecule. Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) holds the potential to improve the accuracy of prostate cancer diagnosis. The aim of this study was to develop a convenient and simple modular strategy for the creation of heterobivalent (HBV) conjugates targeting PSMA/GRPr receptors. For this purpose, we developed and compared six alternative routes for the stereoselective synthesis of HBV conjugates designed to deliver the chelating agent DOTA to PSMA/GRPr receptors. The comparison of these alternative synthetic pathways took into account such factors as efficiency, complexity, synthesis, and purification details, as well as yields of the target compounds. Optimal conditions for the stereoselective synthesis of HBV ligands to PSMA and GRPr, which could serve as molecular platforms for the targeted delivery of therapeutic or diagnostic agents to these receptors, were revealed. For synthesized HBV ligand <b>26</b><sup><b>x</b></sup> and its HBV conjugate with DOTA <b>27</b>, the complete signal assignment in <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N NMR spectra was achieved using 2D NMR techniques. Based on these data, comprehensive signal assignments were provided for all final compounds in their NMR spectra. The final HBV conjugate <b>27</b> was labeled with Lu-177, with yields >99%, and the obtained radiotracer was studied in vitro for its binding specificity, with determining of the <i>K</i><sub>D</sub> and <i>B</i><sub>max</sub> using LNCaP (PSMA+) and PC-3 (GRPr+) cell lines.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770718","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
Self-Assembly of Toll-Like Receptor (TLR2/6) Agonist Lipidated Amino Acid or Peptide Conjugates: Distinct Morphologies and Bioactivities
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-04-02 DOI: 10.1021/acs.bioconjchem.5c0005110.1021/acs.bioconjchem.5c00051
Valeria Castelletto, Lucas R. de Mello, Juliane Pelin and Ian W Hamley*, 
{"title":"Self-Assembly of Toll-Like Receptor (TLR2/6) Agonist Lipidated Amino Acid or Peptide Conjugates: Distinct Morphologies and Bioactivities","authors":"Valeria Castelletto,&nbsp;Lucas R. de Mello,&nbsp;Juliane Pelin and Ian W Hamley*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0005110.1021/acs.bioconjchem.5c00051","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00051https://doi.org/10.1021/acs.bioconjchem.5c00051","url":null,"abstract":"<p >Toll-like receptor (TLR) agonists are of interest in immunotherapy and cancer vaccines. The most common agonists of TLR2 are based on Pam<sub>2</sub>Cys or Pam<sub>3</sub>Cys. In the former, two palmitoyl (Pam) fatty acids are linked to a glycerylcysteine motif by ester linkages. Pam<sub>3</sub>Cys is analogous but contains an extra Pam group on the α-amine. Here, we compare the self-assembly in aqueous solution of the parent Pam<sub>2</sub>CysOH and Pam<sub>3</sub>Cys amino acid conjugates to that of Pam<sub>2</sub>CysSK<sub>4</sub> and Pam<sub>3</sub>CysSK<sub>4</sub> which are potent TLR2 agonists bearing the CysSK<sub>4</sub> peptide sequence. All four conjugates exhibit a critical aggregation concentration above which self-assembled structures are formed. We find through a combination of small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and confocal fluorescence microscopy remarkable differences in self-assembled nanostructures. Pam<sub>2</sub>CysOH and Pam<sub>3</sub>CysOH both form unilamellar vesicles, although these are larger for the latter compound, an effect ascribed to enhanced membrane rigidity. This is in contrast to previously reported morphologies for Pam<sub>2</sub>CysSK<sub>4</sub> and Pam<sub>3</sub>CysSK4, which are spherical micelles or predominantly wormlike micelles, respectively [Hamley, I. W.; et al. <i>Toll-like Receptor Agonist Lipopeptides Self-Assemble into Distinct Nanostructures</i>. Chem. Comm. 2014, 50, 15948-15951]. We also examine the effect of introduction in the bulky <i>N</i>-terminal Fmoc [fluorenylmethoxycarbonyl] group on the self-assembly of Fmoc-Pam<sub>2</sub>CysOH. This compound also forms vesicles (above a critical aggregation concentration, determined from dye probe fluorescence experiments) in aqueous solution, larger than those for Pam<sub>2</sub>CysOH and with a population of perforated/compound vesicles. The carboxyl-coated (and amino-coated for Pam<sub>2</sub>CysOH) vesicles demonstrated here represent a promising system for future development toward bionanotechnology applications such as immune therapies. Conjugates Pam<sub>2</sub>CysOH, Pam<sub>2</sub>CysSK<sub>4</sub>, and Pam<sub>3</sub>CysSK<sub>4</sub> show good cytocompatibility at low concentrations, and in fact, the cell compatibility extends over a wider concentration range for Pam<sub>2</sub>CysOH. The TLR2/6 agonist activity was assessed using an assay that probes secreted alkaline phosphatase (SEAP) in NF-κB-SEAP reporter HEK293 cells expressing human TLR2 and TLR6, and Pam<sub>2</sub>CySOH shows significant activity, although not to the extent of Pam<sub>2</sub>CysSK4 or Pam<sub>3</sub>CysSK<sub>4</sub>. Thus, Pam<sub>2</sub>CysOH in particular is of interest as a vesicle-forming TLR2/6 agonist and stimulator of immune response.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 4","pages":"792–802 792–802"},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.5c00051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832655","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
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
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.5c0003610.1021/acs.bioconjchem.5c00036
Guiquan Zhang, Daming Zhou, Rong Hu*, Anjun Qin* and Ben Zhong Tang*, 
{"title":"Recent Advances in Aggregation-Induced Emission Bioconjugates","authors":"Guiquan Zhang,&nbsp;Daming Zhou,&nbsp;Rong Hu*,&nbsp;Anjun Qin* and Ben Zhong Tang*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0003610.1021/acs.bioconjchem.5c00036","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00036https://doi.org/10.1021/acs.bioconjchem.5c00036","url":null,"abstract":"<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":"36 4","pages":"609–626 609–626"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832790","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.4c0055410.1021/acs.bioconjchem.4c00554
Jean C. Neto, Federico Lucantoni, Leydy V. González, Eva Falomir, Juan F. Miravet and Francisco Galindo*, 
{"title":"Introducing TAPY as a Versatile Alternative to TPP for Selective Mitochondrial Targeting in Cancer Cells","authors":"Jean C. Neto,&nbsp;Federico Lucantoni,&nbsp;Leydy V. González,&nbsp;Eva Falomir,&nbsp;Juan F. Miravet and Francisco Galindo*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0055410.1021/acs.bioconjchem.4c00554","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00554https://doi.org/10.1021/acs.bioconjchem.4c00554","url":null,"abstract":"<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":"36 4","pages":"697–706 697–706"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832574","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
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.5c0010010.1021/acs.bioconjchem.5c00100
Zuohong Chen, Yili Wang, Shaofang Zhang, Huanhuan Qiao, Shuquan Zhang, Hao Wang* and Xiao-Dong Zhang*, 
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