Bioconjugate Chemistry Bioconjugate最新文献

Reactivity Profiling for High-Yielding Ynamine-Tagged Oligonucleotide Click Chemistry Bioconjugations. 高产率Ynamine标记寡核苷酸点击化学生物接合的反应性分析。

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-10 DOI: 10.1021/acs.bioconjchem.4c00353

Frederik Peschke, Andrea Taladriz-Sender, Allan J B Watson, Glenn A Burley

{"title":"Reactivity Profiling for High-Yielding Ynamine-Tagged Oligonucleotide Click Chemistry Bioconjugations.","authors":"Frederik Peschke, Andrea Taladriz-Sender, Allan J B Watson, Glenn A Burley","doi":"10.1021/acs.bioconjchem.4c00353","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00353","url":null,"abstract":"The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a key ligation tool used to prepare bioconjugates. Despite the widespread utility of CuAAC to produce discrete 1,4-triazole products, the requirement of a Cu catalyst can result in oxidative damage to these products. Ynamines are superior reactive groups in CuAAC reactions and require lower Cu loadings to produce 1,4-triazole products. This study discloses a strategy to identify optimal reaction conditions for the formation of oligodeoxyribonucleotide (ODN) bioconjugates. First, the surveying of reaction conditions identified that the ratio of Cu to the choice of reductant (i.e., either sodium ascorbate or glutathione) influences the reaction kinetics and the rate of degradation of bioconjugate products. Second, optimized conditions were used to prepare a variety of ODN-tagged products and ODN-protein conjugates and compared to conventional CuAAC and Cu-free azide-alkyne (3 + 2)cycloadditions (SPAAC), with ynamine-based examples being faster in all cases. The reaction optimization platform established in this study provides the basis for its wider utility to prepare CuAAC-based bioconjugates with lower Cu loadings while maintaining fast reaction kinetics.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386380","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

Comprehensive Review on Bubbles: Synthesis, Modification, Characterization and Biomedical Applications. 关于气泡的全面综述：气泡的合成、改性、表征和生物医学应用。

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-08 DOI: 10.1021/acs.bioconjchem.4c00137

Donald A Fernandes

引用次数: 0

Inhibitory Effects on RNA Binding and RNase H Induction Activity of Prodrug-Type Oligodeoxynucleotides Modified with a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase 用可被β-半乳糖苷酶裂解的半乳糖化自消旋连接体修饰的原药型寡脱氧核苷酸对 RNA 结合和 RNase H 诱导活性的抑制作用

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-08 DOI: 10.1021/acs.bioconjchem.4c0037610.1021/acs.bioconjchem.4c00376

Kento Miyaji, Yoshiaki Masaki and Kohji Seio*,

{"title":"Inhibitory Effects on RNA Binding and RNase H Induction Activity of Prodrug-Type Oligodeoxynucleotides Modified with a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase","authors":"Kento Miyaji, Yoshiaki Masaki and Kohji Seio*, ","doi":"10.1021/acs.bioconjchem.4c0037610.1021/acs.bioconjchem.4c00376","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00376https://doi.org/10.1021/acs.bioconjchem.4c00376","url":null,"abstract":"Prodrug-type oligonucleotides (prodrug-ONs) are a class of oligonucleotide designed for activation under specific intracellular conditions or external stimuli. Prodrug-ONs can be activated in the target tissues or cells, thereby reducing the risk of adverse effects. In this study, we synthesized prodrug-type oligodeoxynucleotides activated by β-galactosidase, an enzyme that is overexpressed in cancer and senescent cells. These oligodeoxynucleotides (ODNs) contain a modified thymidine conjugated with galactose via a self-immolative linker at the O4-position. UV-melting analysis revealed that the modifications decreased the melting temperature (Tm) compared with that of the unmodified ODN when hybridized with complementary RNA. Furthermore, cleavage of the glycosidic bond by β-galactosidase resulted in the spontaneous removal of the linker from the nucleobase moiety, generating unmodified ODNs. Additionally, the introduction of multiple modified thymidines into ODNs completely inhibited the RNase H-mediated cleavage of complementary RNA. These findings suggest the possibility of developing prodrug-ONs, which are specifically activated in cancer cells or senescent cells with high β-galactosidase expression.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437106","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

Inhibitory Effects on RNA Binding and RNase H Induction Activity of Prodrug-Type Oligodeoxynucleotides Modified with a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase. 用可被β-半乳糖苷酶裂解的半乳糖化自消旋连接体修饰的原药型寡脱氧核苷酸对 RNA 结合和 RNase H 诱导活性的抑制作用

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-08 DOI: 10.1021/acs.bioconjchem.4c00376

Kento Miyaji, Yoshiaki Masaki, Kohji Seio

{"title":"Inhibitory Effects on RNA Binding and RNase H Induction Activity of Prodrug-Type Oligodeoxynucleotides Modified with a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase.","authors":"Kento Miyaji, Yoshiaki Masaki, Kohji Seio","doi":"10.1021/acs.bioconjchem.4c00376","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00376","url":null,"abstract":"Prodrug-type oligonucleotides (prodrug-ONs) are a class of oligonucleotide designed for activation under specific intracellular conditions or external stimuli. Prodrug-ONs can be activated in the target tissues or cells, thereby reducing the risk of adverse effects. In this study, we synthesized prodrug-type oligodeoxynucleotides activated by β-galactosidase, an enzyme that is overexpressed in cancer and senescent cells. These oligodeoxynucleotides (ODNs) contain a modified thymidine conjugated with galactose via a self-immolative linker at the O4-position. UV-melting analysis revealed that the modifications decreased the melting temperature (Tm) compared with that of the unmodified ODN when hybridized with complementary RNA. Furthermore, cleavage of the glycosidic bond by β-galactosidase resulted in the spontaneous removal of the linker from the nucleobase moiety, generating unmodified ODNs. Additionally, the introduction of multiple modified thymidines into ODNs completely inhibited the RNase H-mediated cleavage of complementary RNA. These findings suggest the possibility of developing prodrug-ONs, which are specifically activated in cancer cells or senescent cells with high β-galactosidase expression.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386379","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

Drug Delivery Targeting Neuroinflammation to Treat Brain Diseases. 针对神经炎症的药物输送治疗脑部疾病。

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-08 DOI: 10.1021/acs.bioconjchem.4c00414

Juntao Wang, Ruiqin Jia, Wubo Wan, Haijun Han, Guoying Wang, Zhen Li, Jia Li

引用次数: 0

A Novel Bifunctional Chelating Agent for Tyrosine-Specific Radiolabeling of Peptides and Proteins. 用于肽和蛋白质酪氨酸特异性放射性标记的新型双功能螯合剂

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-07 DOI: 10.1021/acs.bioconjchem.4c00363

Daiki Nakano, Hiroyuki Watanabe, Saito Kosuke, Masahiro Ono

{"title":"A Novel Bifunctional Chelating Agent for Tyrosine-Specific Radiolabeling of Peptides and Proteins.","authors":"Daiki Nakano, Hiroyuki Watanabe, Saito Kosuke, Masahiro Ono","doi":"10.1021/acs.bioconjchem.4c00363","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00363","url":null,"abstract":"Site-specific radiolabeling is utilized for the development of antibody- or peptide-based radiotheranostic agents. Although tyrosine can be exploited as one of the target residues for site-specific radiolabeling of peptides and proteins, a tyrosine-specific radiolabeling method has not been established. In this study, we newly designed and synthesized a novel bifunctional chelating agent, TBD-DO3A, consisting of a triazabutadiene (TBD) scaffold and metal chelator, 1,4,7,10-tetraazacyclododecane 1,4,7-triacetic acid (DO3A). Conjugation of TBD-DO3A with Ac-Tyr-NHMe followed by 111In-labeling afforded [111In]In-Tyr-DO3A, which showed high-level stability in mouse plasma. Then, we selected the tyrosine-containing cyclic peptide c(RGDyK) as a model ligand and synthesized [111In]In-RYD. [111/natIn]In-RYD showed in vitro binding properties for integrin αvβ3 equivalent to those of [111/natIn]In-RKD, a lysine residue-labeled control compound. In in vivo biodistribution and SPECT/CT imaging studies using U87MG/PC-3 tumor-bearing mice, [111In]In-RYD and [111In]In-RKD were selectively accumulated and facilitated U87MG tumor visualization at 24 h postinjection. These results indicate that TBD-DO3A has fundamental properties as a bifunctional chelator for tyrosine-specific radiolabeling of peptides and proteins.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379460","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

A Novel Bifunctional Chelating Agent for Tyrosine-Specific Radiolabeling of Peptides and Proteins 用于肽和蛋白质酪氨酸特异性放射性标记的新型双功能螯合剂

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-07 DOI: 10.1021/acs.bioconjchem.4c0036310.1021/acs.bioconjchem.4c00363

Daiki Nakano, Hiroyuki Watanabe*, Saito Kosuke and Masahiro Ono*,

{"title":"A Novel Bifunctional Chelating Agent for Tyrosine-Specific Radiolabeling of Peptides and Proteins","authors":"Daiki Nakano, Hiroyuki Watanabe*, Saito Kosuke and Masahiro Ono*, ","doi":"10.1021/acs.bioconjchem.4c0036310.1021/acs.bioconjchem.4c00363","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00363https://doi.org/10.1021/acs.bioconjchem.4c00363","url":null,"abstract":"Site-specific radiolabeling is utilized for the development of antibody- or peptide-based radiotheranostic agents. Although tyrosine can be exploited as one of the target residues for site-specific radiolabeling of peptides and proteins, a tyrosine-specific radiolabeling method has not been established. In this study, we newly designed and synthesized a novel bifunctional chelating agent, TBD-DO3A, consisting of a triazabutadiene (TBD) scaffold and metal chelator, 1,4,7,10-tetraazacyclododecane 1,4,7-triacetic acid (DO3A). Conjugation of TBD-DO3A with Ac-Tyr-NHMe followed by 111In-labeling afforded [111In]In-Tyr-DO3A, which showed high-level stability in mouse plasma. Then, we selected the tyrosine-containing cyclic peptide c(RGDyK) as a model ligand and synthesized [111In]In-RYD. [111/natIn]In-RYD showed in vitro binding properties for integrin αvβ3 equivalent to those of [111/natIn]In-RKD, a lysine residue-labeled control compound. In in vivo biodistribution and SPECT/CT imaging studies using U87MG/PC-3 tumor-bearing mice, [111In]In-RYD and [111In]In-RKD were selectively accumulated and facilitated U87MG tumor visualization at 24 h postinjection. These results indicate that TBD-DO3A has fundamental properties as a bifunctional chelator for tyrosine-specific radiolabeling of peptides and proteins.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437266","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

Identification of a Novel Transasparaginase Activity of Bacillus subtilis (bTG) for Sequence-Specific Bioconjugation 鉴定枯草芽孢杆菌（bTG）用于序列特异性生物连接的新型转天冬酰胺酶活性

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-03 DOI: 10.1021/acs.bioconjchem.4c0030610.1021/acs.bioconjchem.4c00306

Marie Flamme*, Raphael Göhring, Denise Zamarbide, Corentin Bon, Alexandra Vissières, Anne Basler, Daniela Miranda, Rainer Kneuer and Greg Mann*,

{"title":"Identification of a Novel Transasparaginase Activity of Bacillus subtilis (bTG) for Sequence-Specific Bioconjugation","authors":"Marie Flamme*, Raphael Göhring, Denise Zamarbide, Corentin Bon, Alexandra Vissières, Anne Basler, Daniela Miranda, Rainer Kneuer and Greg Mann*, ","doi":"10.1021/acs.bioconjchem.4c0030610.1021/acs.bioconjchem.4c00306","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00306https://doi.org/10.1021/acs.bioconjchem.4c00306","url":null,"abstract":"The ability of Bacillus subtilis transglutaminase (bTG) to functionalize BSA has been investigated using peptide mapping experiments. Interestingly, the conjugation was not detected on a glutamine but on an asparagine residue. A sequence determination study was further performed, and a sequence of 10 amino acids for site-specific conjugation was identified. A monobody showing no native reactivity with the bTG enzyme was produced with the identified peptide sequences and successfully conjugated to various types of substrates in very high yields (>90%) with a 1/1/1.5 ratio of protein/amine/enzyme. Direct conjugation to the amino linker of a small interfering RNA (siRNA) was achieved in good yield, and no impact on the siRNA activity was observed following the conjugation. The identified sequences were further engineered in VHH and IgG scaffolds, and successful conjugation could also be observed with both small molecules and siRNA, confirming the potential of bTG for site-specific enzymatic bioconjugation.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436774","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

Linker and Conjugation Site Synergy in Antibody–Drug Conjugates: Impacts on Biological Activity 抗体-药物共轭物中连接体和共轭位点的协同作用：对生物活性的影响

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-03 DOI: 10.1021/acs.bioconjchem.4c0034810.1021/acs.bioconjchem.4c00348

Michihiko Aoyama*, Minoru Tada, Hidetomo Yokoo, Takahito Ito, Takashi Misawa, Yosuke Demizu and Akiko Ishii-Watabe,

{"title":"Linker and Conjugation Site Synergy in Antibody–Drug Conjugates: Impacts on Biological Activity","authors":"Michihiko Aoyama*, Minoru Tada, Hidetomo Yokoo, Takahito Ito, Takashi Misawa, Yosuke Demizu and Akiko Ishii-Watabe, ","doi":"10.1021/acs.bioconjchem.4c0034810.1021/acs.bioconjchem.4c00348","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00348https://doi.org/10.1021/acs.bioconjchem.4c00348","url":null,"abstract":"Antibody–drug conjugates (ADCs) produced using general conjugation methods yield heterogeneous products containing mixtures of species with different numbers of payloads per antibody (drug–antibody ratios) conjugated at multiple sites. This heterogeneity affects the stability, efficacy, and safety of ADCs. Thus, various site-specific conjugation methods have been developed to achieve homogeneity in ADCs. It was reported that linker structures and conjugation sites generally affected the characteristics of site-specific ADCs such as stability, efficacy, and safety. However, the combined effects of conjugation sites and linker structures on the physicochemical and biological characteristics of site-specific ADCs have remained unclear. In this study, we generated 30 homogeneous site-specific ADCs with a combination of six conjugation sites and five linker structures using THIOMAB technology and evaluated the characteristics of these homogeneous ADCs. We found that both conjugation sites and linker structures affected characteristics unique to ADCs (linker stability as well as target-dependent and target-independent cytotoxicity) in site-specific ADCs. Especially, conjugation to the constant regions of the light chain and the presence of polyethylene glycol structures in the linker are important for those ADC-specific characteristics. Interestingly, we also found that the effects of linker structures on the target-independent cytotoxicity of homogeneous ADCs at certain conjugation sites differed from those seen in conventional heterogeneous ADCs. Our results suggest that optimizing linker structures based on the conjugation site may be necessary for site-specific ADCs.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436781","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

Equimolar Cross-Coupling Using Reactive Coiled Coils for Covalent Protein Assemblies 利用反应性线圈实现共价蛋白质组装的等摩尔交叉耦合

IF 4 2区化学

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-10-03 DOI: 10.1021/acs.bioconjchem.4c0032710.1021/acs.bioconjchem.4c00327

Hironori Takeuchi, Elee Shimshoni, Satish Gandhesiri, Andrei Loas and Bradley L. Pentelute*,

{"title":"Equimolar Cross-Coupling Using Reactive Coiled Coils for Covalent Protein Assemblies","authors":"Hironori Takeuchi, Elee Shimshoni, Satish Gandhesiri, Andrei Loas and Bradley L. Pentelute*, ","doi":"10.1021/acs.bioconjchem.4c0032710.1021/acs.bioconjchem.4c00327","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00327https://doi.org/10.1021/acs.bioconjchem.4c00327","url":null,"abstract":"Biocompatible cross-coupling reactions enable the efficient covalent attachment of large biomolecules at near-stoichiometric ratios, ensuring the stability and integrity of the resulting products. We present an affinity-based peptide platform utilizing coiled coils containing reactive side chains for proximity-driven protein cross-coupling in the presence of a cross-linking agent. This platform supports both chemical synthesis and recombinant expression, using canonical amino acids to generate reactive affinity tags. Employing the E3/R3 coiled coil pair as a scaffold, we design four complementary coils with cysteine residues as cross-linking sites, achieving >90% conversion to covalent heterodimeric coupling products using 3,4-dibromomaleimide. Equimolar mixtures of proteins with reactive coils at their termini yield near-quantitative heterodimeric cross-coupling products. The strategic selection of complementary coiled coil pairs and cross-linking agents enables orthogonal assembly of macromolecules with diverse architectures. This method offers a versatile approach for creating covalent fusion proteins, enhancing their stability and functionality for applications in chemical biology, biotechnology, and medicine.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436555","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