RSC Chemical Biology最新文献

{"title":"Halogenation of nucleic acid structures: from chemical biology to supramolecular chemistry","authors":"Catalina Nicolau, Julia Requena-Ramírez, Jorge González-García and Antonio Bauzá","doi":"10.1039/D5CB00077G","DOIUrl":"10.1039/D5CB00077G","url":null,"abstract":"<p >Halogenation of organic molecules is a widespread resource used in the fields of chemical biology and rational drug design to improve the binding affinity or solubility of a given compound. Interestingly, the incorporation of Br and I in DNA/RNA bases has been routinely carried out during decades to facilitate the structural determination of nucleic acids, without accounting for its impact in the DNA/RNA structure and molecular recognition events involving other biological entities (<em>e.g.</em> proteins and peptides). This is of critical importance, since halogens undergo non-covalent binding (specially Br and I) through the formation of halogen bonding interactions, thus structurally influencing peptide/protein–DNA/RNA binding poses or altering the supramolecular architecture of isolated nucleic acid structures. In this review, the physical nature of halogen bonds involving nucleobases as well as their implications in (i) the formation of protein–DNA/RNA complexes and (ii) the stabilization of non-canonical DNA/RNA structures will be discussed, focusing on the role of this non-covalent interaction as a promising tool in nucleic acid chemistry.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1007-1018"},"PeriodicalIF":4.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the role of key amino acid residues of the parainfluenza fusion peptide in membrane fusion","authors":"Mariana Valério, Carolina C. Buga, Diogo A. Mendonça, Miguel A. R. B. Castanho, Manuel N. Melo, Cláudio M. Soares, Diana Lousa and Ana Salomé Veiga","doi":"10.1039/D5CB00058K","DOIUrl":"10.1039/D5CB00058K","url":null,"abstract":"<p >Parainfluenza viruses enter host cells by fusing their envelope with the cell membrane. In this process mediated by the fusion glycoprotein, the fusion peptide plays an essential role in membrane binding and triggering fusion. Previously, we demonstrated that the parainfluenza fusion peptide (PIFP) oligomerizes into porelike structures within the membrane, leading to membrane perturbations, fusion, and leakage. Additionally, we identified two key amino acid residues in the PIFP, F103 and Q120, which are important in inducing lipid tail protrusion and maintaining peptide–peptide interactions, respectively. Here, we seek to elucidate the role of these two residues in the PIFP function by studying the impact of F103A and Q120A substitutions on peptide activity. We compared the substituted peptides with the native peptide using biophysical experiments and molecular dynamics (MD) simulations. Our results show that the F103A substitution significantly impairs PIFP's interaction with the membrane and its ability to induce lipid mixing and membrane leakage in experimental assays. Moreover, a decrease in lipid perturbation and water flux through the membrane was observed in the MD simulations. In contrast, the Q120A substitution appears to have minimal impact on membrane interaction and PIFP-induced membrane leakage. Interestingly, a pronounced change in the interpeptide interactions within the membrane of the substituted peptides was observed in the MD simulations. These findings provide crucial insights into the potential role of F103 and Q120 in PIFP activity: the N-terminal phenylalanine (F103) is pivotal for membrane insertion and fusion, while the Q120 is crucial for regulating peptide oligomerization and pore formation.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1100-1114"},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroglutathione, a glutathione derivative to introduce non-reversible glutathionylation†","authors":"Daniel Oppong, Rayavarapu Padmavathi, Dhanushika S. K. Kukulage, Madhu C. Shivamadhu, Elizabeth A. Newberry, Anneliese M. Faustino, Hsin-Yao Tang and Young-Hoon Ahn","doi":"10.1039/D5CB00052A","DOIUrl":"10.1039/D5CB00052A","url":null,"abstract":"<p >Protein cysteine is susceptible to diverse oxidations, including disulfide, <em>S</em>-sulfenylation, <em>S</em>-nitrosylation, and <em>S</em>-glutathionylation, that regulate many biological processes in physiology and diseases. Despite evidence supporting distinct biological outcomes of individual cysteine oxoforms, the approach for examining functional effects resulting from a specific cysteine oxoform, such as <em>S</em>-glutathionylation, remains limited. In this report, we devised a dehydroglutathione (dhG)-mediated strategy, named G-PROV, that introduces a non-reducible glutathionylation mimic to the protein with the subsequent delivery of the modified protein to cells to examine the “phenotype” attributed to “glutathionylation”. We applied our strategy to fatty acid binding protein 5 (FABP5), demonstrating that dhG induces selective modification at C127 of FABP5, resembling <em>S</em>-glutathionylation. dhG-modified glutathionylation in FABP5 increases its binding affinity to linoleic acid, enhances its translocation to the nucleus for activating PPARβ/δ, and promotes MCF7 cell migration in response to linoleic acid. Our data report a facile chemical tool to introduce a glutathionylation mimic to proteins for functional analysis of protein glutathionylation.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1156-1164"},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RaPID discovery of cell-permeable helical peptide inhibitors con-taining cyclic β-amino acids against SARS-CoV-2 main protease†","authors":"Marina Kawai, Tika R. Malla, H. T. Henry Chan, Anthony Tumber, Lennart Brewitz, Eidarus Salah, Naohiro Terasaka, Takayuki Katoh, Akane Kawamura, Christopher J. Schofield, Fernanda Duarte and Hiroaki Suga","doi":"10.1039/D5CB00021A","DOIUrl":"10.1039/D5CB00021A","url":null,"abstract":"<p >Structurally constrained cyclic β-amino acids are attractive building blocks for peptide drugs because they induce unique and stable conformations. Introduction of (1<em>S</em>,2<em>S</em>)-2-aminocyclopentanecarboxylic acid [(1<em>S</em>,2<em>S</em>)-2-ACPC] into peptides stabilizes helical conformations, so improving proteolytic stability and cell membrane permeability. We report on the ribosomal synthesis of a helical peptide library incorporating (1<em>S</em>,2<em>S</em>)-2-ACPC at every third position and its application for the discovery of SARS-CoV-2 main protease (M<small>^pro</small>) inhibitors. We identified two peptide sequences containing multiple (1<em>S</em>,2<em>S</em>)-2-ACPC residues, which exhibit helical conformations and superior proteolytic stability compared with their α-Ala or β-Ala counterparts. Studies using the chloroalkane cell-penetration assay showed that their cell permeability values (CP<small>₅₀</small>) are comparable with or even slightly better than that of the cell-penetrating nona-arginine (R9) peptide. The new approach is thus a highly efficient method that combines a helical peptide library containing structurally constrained cyclic β-amino acids with the classical RaPID discovery method, enabling <em>de novo</em> discovery of proteolytically stable and cell-penetrating bioactive peptides that target intracellular proteins.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1089-1099"},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A general and accessible approach to enrichment and characterisation of natural anti-Neu5Gc antibodies from human samples†","authors":"Esme Hutton, Yumiko Uno, Emma Scott, Craig Robson, Martin A. Fascione and Nathalie Signoret","doi":"10.1039/D5CB00073D","DOIUrl":"10.1039/D5CB00073D","url":null,"abstract":"<p > <em>N</em>-Glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid which is presented on the surface of human cells following uptake from dietary sources. Antibodies against Neu5Gc have implications for many aspects of human health such as inflammation, xenograft rejection and cancer. However, current methods to detect and study anti-Neu5Gc antibodies require complex synthesis of glycan structures, animal handling expertise, or access to expensive reagents and equipment. Here, we outline a simple workflow to enrich and detect anti-Neu5Gc antibodies from small volume human serological samples. This strategy involves a micro-scale affinity purification step, followed by an indirect ELISA detection step which uses CMAH-transfected human cells as a source of Neu5Gc-containing human glycans in their native context. Parental wild type cells are also used as a paired Neu5Gc-negative control. Using this workflow, Neu5Gc-specific antibodies could be enriched from intravenous immunoglobulin (IVIG) and individual plasma specimens from ten healthy donors. Anti-Neu5Gc antibodies were detected in all donors, regardless of age or sex. The lysate ELISA assay was also sufficiently sensitive to observe reproducible individual differences in the anti-Neu5Gc reactivity of each donor specimen. Importantly, despite this individual variation, enriched antibodies from all donor specimens bound effectively to Neu5Gc-containing glycans presented on the surface of whole human cells, highlighting the potential physiological relevance of these antibodies.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1135-1147"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turn-on fluorescent glucose transport bioprobe enables wash-free real-time monitoring of glucose uptake activity in live cells and small organisms†","authors":"Monica S. Hensley, David Hutchings, Aldelrahman Ismail and Marina Tanasova","doi":"10.1039/D4CB00239C","DOIUrl":"10.1039/D4CB00239C","url":null,"abstract":"<p >The direct link between sugar uptake and metabolic diseases highlights the iminent need for molecular tools to detect and evaluate alterations in sugar uptake efficiency as approaches to identify disease-relevant metabolic alterations. However, the strict requirements of facilitative glucose transporters regarding substrate binding and translocation pose challenges for developing effective fluorescence molecular probes. Based on the state-of-the-art understanding of glucose recognition by facilitative transporters (GLUTs), we designed a glucopyranoside mimic – GluRho – that delivers the “turn-on” rhodamine B to live cells <em>via</em> glucose transport, including major transporters GLUTs 1–4. The high binding affinity achieved through the secondary interaction between the fluorophore and a GLUT protein supports the delivery of the probe in nutrient-rich conditions, facilitating its use as a tool for a direct assessment of glucose GLUT activity in live cells and organisms and across various experimental settings, including uptake evaluation in the presence of sugars or GLUT activity modulators. The lack of metabolic contribution to the probe uptake due to the elimination of the phosphorylation site contributes to the high efficacy of the GluRho probe in reflecting alterations in glucose uptake efficiency in live cells, between cell lines, and in multicellular model organisms, such as <em>Drosophila melanogaster</em>. The molecular modeling analysis of GluRho complexes with GLUT1 and GLUT2 provided essential information on GLUT-probe interactions, highlighting the residues facilitating the effective binding and translocation of the probe through transporters, thus setting the basis for developing glucose-based glycoconjugates as a cargo-delivering platform.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 987-995"},"PeriodicalIF":4.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into the ATP-mediated and species-dependent inhibition of TrpRS by chuangxinmycin†","authors":"Yichen Ren, Sili Wang, Wen Liu, Jing Wang and Pengfei Fang","doi":"10.1039/D5CB00060B","DOIUrl":"10.1039/D5CB00060B","url":null,"abstract":"<p >Chuangxinmycin (CXM) is a promising antimicrobial compound targeting bacterial tryptophanyl-tRNA synthetase (TrpRS), an essential enzyme in protein synthesis. The detailed inhibitory mechanism of CXM, particularly in clinically relevant pathogenic bacteria, is poorly understood. In this study, based on the determination of 10 crystal structures, including <em>Escherichia coli</em> TrpRS (<em>Ec</em>TrpRS) and <em>Staphylococcus aureus</em> TrpRS (<em>Sa</em>TrpRS) in complex with CXM, ATP, tryptophan, or CXM derivatives, either individually or in combination, as well as the structure of apo-<em>Sa</em>TrpRS, we provide key insights into the binding mode of CXM and its species-specific inhibitory mechanisms. Combined with molecular dynamics simulations and binding energy analysis, we demonstrate that CXM binds to <em>Ec</em>TrpRS in a manner highly similar to the natural substrate tryptophan. Key residues, including D135 and Y128, play critical roles in CXM recognition and fixation, while conserved hydrophobic residues contribute significantly to binding free energy. This binding pattern is consistent with that observed in <em>Geobacillus stearothermophilus</em> TrpRS (<em>Gs</em>TrpRS). However, <em>Sa</em>TrpRS exhibits distinct behavior due to structural differences, particularly the orientation of Y126 (corresponding to Y128 in <em>Ec</em>TrpRS). This difference results in the selectivity of 3-methylchuangxinmycin (mCXM), a CXM derivative, against <em>Sa</em>TrpRS. Furthermore, modeling CXM into the tryptophan-binding site of human cytoplasmic TrpRS (<em>Hs</em>TrpRS) reveals the lack of key hydrogen bonds and a salt bridge interaction, which likely underlies CXM's significantly weaker inhibition of <em>Hs</em>TrpRS. These findings deepen our understanding of the inhibitory mechanism of CXM and its selectivity toward bacterial TrpRSs, and thus can facilitate the design of next-generation antibiotics targeting bacterial TrpRSs.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1079-1088"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cysteine sulfinic acid and sulfinylated peptides","authors":"Laura Hayward and Matthias G. J. Baud","doi":"10.1039/D5CB00040H","DOIUrl":"10.1039/D5CB00040H","url":null,"abstract":"<p >Cysteine sulfinic acid (CSA) is a stable post translational modification in nature. While long considered to be an irreversible by-product of accidental overoxidation of the cysteine sulfur, evidence in the last two decades has accumulated for its role in numerous and tightly regulated mechanisms. Proteomics studies in the last two decades have identified CSA in hundreds of cellular proteins, highlighting its omnipresence at the core of the cysteine redoxome. Elsewhere, structural studies have shed initial light on the molecular mechanisms underlying CSA reduction <em>in vivo</em> by the sulfiredoxin (Srx) enzyme. While peroxiredoxins have for a long time been the only known substrates to be turned over by Srx, recent studies have uncovered a plethora of potential new substrates of Srx, opening new avenues of investigation in fundamental biology, but also possibly opening new opportunities for developing novel medicines targeting the redoxome, especially in cancer and neurodegeneration. This review first summarises important knowledge surrounding the stereo-electronics and biochemical properties of CSA, including how it is reduced by Srx. In a second part, it highlights the chemical methods recently developed for CSA characterisation, with important examples of electrophilic probes for CSA covalent adduct formation. Crucially, <em>in vitro</em> biochemical studies of CSA and its peptides have historically proven difficult, in great part due to the limitations associated with the few existing synthetic methods available. Here, we also provide a summary of synthetic methods currently available for CSA incorporation into peptides, and their current limitations.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1019-1033"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering regiospecific methylation of the pladienolides†","authors":"Emily R. Smith, Dua H. Al-Smadi, Yitao Dai, Manead Khin, Joanna E. Burdette, Brendan M. Duggan, James J. La Clair, Alessandra S. Eustáquio and Michael D. Burkart","doi":"10.1039/D5CB00068H","DOIUrl":"10.1039/D5CB00068H","url":null,"abstract":"<p >Well-recognized for the ability to modulate spliceosome activity, the pladienolide family of polyketide natural products has been the recent subject of intense synthetic and bioactivity studies. However, our understanding of their biosynthesis remains incomplete. Here, we report the biosynthetic gene cluster of FD-895 from <em>Streptomyces hygroscopicus</em> A-9561 and explore the installation of a key methylation important for metabolite stability. We demonstrate the <em>in vitro</em> and <em>in vivo</em> application of an <em>O</em>-methyltransferase for regioselective methylation of pladienolide B at the C21 position, a post-synthase modification critical for compound stability. These findings provide a crucial next step in developing systems to engineer this important family of splicing modulatory anti-tumor agents.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1126-1134"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An iridium(iii) 3-chloro-6-thio-1,2,4,5-tetrazine complex for cysteine conjugation, bioimaging and photoactivated therapy†","authors":"Lili Huang, Justin Shum, Lawrence Cho-Cheung Lee, Guang-Xi Xu, Peter Kam-Keung Leung and Kenneth Kam-Wing Lo","doi":"10.1039/D4CB00316K","DOIUrl":"10.1039/D4CB00316K","url":null,"abstract":"<p >Photoactivatable systems have received considerable attention in the development of diagnostics and therapeutics due to their noninvasive nature and precise spatiotemporal control. Of particular interest is the 3,6-dithio-1,2,4,5-tetrazine (<em>S</em>,<em>S</em>-tetrazine) unit, which can not only act as a photolabile protecting group for constructing photoactivatable systems but also as a bioorthogonal scaffold that enables the inverse electron-demand Diels–Alder (IEDDA) cycloaddition reaction with strained alkynes. In this study, we designed and synthesised a cyclometallated iridium(<small>III</small>) complex modified with a 3-chloro-6-thio-1,2,4,5-tetrazine moiety (<strong>1</strong>) for cysteine conjugation. The complex was conjugated with an integrin-targeting peptide c(RGDfC) to afford a tumour-targeting conjugate (<strong>1-RGD</strong>) for bioimaging and photoactivated therapy. An RGD-free analogue (<strong>2</strong>) was also prepared for comparison studies. Unlike common iridium(<small>III</small>) complexes, excitation of conjugate <strong>1-RGD</strong> and complex <strong>2</strong> resulted in weak emission and negligible singlet oxygen (<small>¹</small>O<small>₂</small>) generation due to the quenching effect of the tetrazine unit. Upon continuous light irradiation, the <em>S</em>,<em>S</em>-tetrazine moiety in conjugate <strong>1-RGD</strong> and complex <strong>2</strong> underwent efficient photodissociation, yielding thiocyanate (<strong>3</strong>) and amide (<strong>4</strong>) complexes as photoproducts with increased emission intensities and enhanced <small>¹</small>O<small>₂</small> generation efficiencies. Interestingly, the IEDDA cycloaddition reaction of the <em>S</em>,<em>S</em>-tetrazine-containing conjugate <strong>1-RGD</strong> and complex <strong>2</strong> with (1<em>R</em>,8<em>S</em>,9<em>s</em>)-bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) led to significant emission enhancement. Notably, conjugate <strong>1-RGD</strong> showed higher cellular uptake and (photo)cytotoxicity (IC<small>_50,dark</small> = 26 μM, IC<small>_50,light</small> = 0.08 μM) in U87-MG cells, which overexpress integrin, compared to MCF-7 (IC<small>_50,dark</small> = 52 μM, IC<small>_50,light</small> = 0.22 μM) and HEK293 cells (IC<small>_50,dark</small> &gt; 50 μM, IC<small>_50,light</small> = 1.3 μM) with lower integrin levels. This work will contribute to the development of photoactivatable transition metal complexes for cancer-targeted imaging and therapy.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1148-1155"},"PeriodicalIF":4.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}