Pub Date : 2024-09-20DOI: 10.1021/acs.bioconjchem.4c00391
Priya Ranjan Sahoo, Joseph A. Spernyak, Steven G. Turowski, Janet R. Morrow
A T1 MRI probe based on a self-assembled coordination cage with four iron(III) centers acts as a host for the hydrolysis product of the gold(I) anticancer drug, Au(PEt3)Cl. 1H NMR characterization of the gold complex encapsulated within the diamagnetic Ga(III) analog of the coordination cage is consistent with loss of chloride to give aquated gold complex, most likely [Au(PEt3)(OH2)]+ within the cage. The gold complex undergoes pH-dependent speciation changes in the Ga(III) cage and is released at mildly acidic pH from both the Ga(III) and Fe(III) cages. NMR spectroscopy studies of the encapsulated gold complex in the presence of human serum albumin (HSA) show that the gold complex remains inside of the Ga(III) cage for several hours, resisting release and binding to cysteine residues of HSA. The Fe(III) cage with encapsulated gold complex shows enhanced contrast of the vasculature and uptake into CT26 tumors in BALB/c mice as shown by MRI. The gold complex is solubilized by the iron(III) cage for intravenous injection, whereas the free complex must be injected intraperitoneally. Gold complex accumulates in the tumor for both caged and free complex over 1–48 h as measured by ex-vivo analysis. Encapsulation in the Fe(III) cage modulates the biodistribution of the gold complex in mice in comparison to the free complex, consistent with the function of the cage as a carrier.
{"title":"Self-Assembled Iron(III) Coordination Cage as an MRI-Active Carrier for a Gold(I) Drug","authors":"Priya Ranjan Sahoo, Joseph A. Spernyak, Steven G. Turowski, Janet R. Morrow","doi":"10.1021/acs.bioconjchem.4c00391","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00391","url":null,"abstract":"A T<sub>1</sub> MRI probe based on a self-assembled coordination cage with four iron(III) centers acts as a host for the hydrolysis product of the gold(I) anticancer drug, Au(PEt<sub>3</sub>)Cl. <sup>1</sup>H NMR characterization of the gold complex encapsulated within the diamagnetic Ga(III) analog of the coordination cage is consistent with loss of chloride to give aquated gold complex, most likely [Au(PEt<sub>3</sub>)(OH<sub>2</sub>)]<sup>+</sup> within the cage. The gold complex undergoes pH-dependent speciation changes in the Ga(III) cage and is released at mildly acidic pH from both the Ga(III) and Fe(III) cages. NMR spectroscopy studies of the encapsulated gold complex in the presence of human serum albumin (HSA) show that the gold complex remains inside of the Ga(III) cage for several hours, resisting release and binding to cysteine residues of HSA. The Fe(III) cage with encapsulated gold complex shows enhanced contrast of the vasculature and uptake into CT26 tumors in BALB/c mice as shown by MRI. The gold complex is solubilized by the iron(III) cage for intravenous injection, whereas the free complex must be injected intraperitoneally. Gold complex accumulates in the tumor for both caged and free complex over 1–48 h as measured by ex-vivo analysis. Encapsulation in the Fe(III) cage modulates the biodistribution of the gold complex in mice in comparison to the free complex, consistent with the function of the cage as a carrier.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1021/acs.bioconjchem.4c00396
Wei Liu, Sufei Zhou, Ke Yang, Di Liu, Yuxing Yan, Fangzhen Tian, Tianyi Cui, Wei Wang, Lewei Bi, Lan Li, Hao Wang, Xiao-Dong Zhang
Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.
{"title":"Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection","authors":"Wei Liu, Sufei Zhou, Ke Yang, Di Liu, Yuxing Yan, Fangzhen Tian, Tianyi Cui, Wei Wang, Lewei Bi, Lan Li, Hao Wang, Xiao-Dong Zhang","doi":"10.1021/acs.bioconjchem.4c00396","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00396","url":null,"abstract":"Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1021/acs.bioconjchem.4c00309
Irene Shajan, Léa N. C. Rochet, Shannon R. Tracey, Rania Benazza, Bianka Jackowska, Oscar Hernandez-Alba, Sarah Cianférani, Christopher J. Scott, Floris L. van Delft, Vijay Chudasama, Bauke Albada
Redirecting T cells to tumor cells by bispecific antibodies is an effective approach to treat cancer, and T cell-dependent bispecific antibodies (TDBAs) are an emerging class of potent immunotherapeutic agents. By simultaneously targeting antigens on tumor cells and T cells, T cells are activated to kill tumor cells. Herein, we report a platform to generate a novel class of 2:1 structure of T cell-dependent bispecific antibody with bivalency for HER2 receptors on tumor cells and monovalency for CD3 receptors on T cells. For this, we use a biogenic inverse electron-demand Diels–Alder (IEDDA) click reaction on genetically encoded tyrosine residues to install one TCO handle on therapeutically approved antibody trastuzumab. Subsequent TCO-tetrazine click with a tetrazine-functionalized CD3-binding Fab yields a 2:1 HER2 × CD3 TDBA that exhibits a tumor-killing capability at picomolar concentrations. Monovalency toward the CD3 receptor on T cells can lower the chances of cytokine release syndrome, which is a common side effect of such agents. Our semisynthetic approach can generate highly potent TDBA constructs in a few chemoenzymatic and synthetic steps.
通过双特异性抗体将 T 细胞重新导向肿瘤细胞是治疗癌症的有效方法，而 T 细胞依赖性双特异性抗体（TDBAs）是一类新兴的强效免疫治疗药物。通过同时靶向肿瘤细胞和 T 细胞上的抗原，T 细胞被激活，从而杀死肿瘤细胞。在此，我们报告了一种生成新型 2:1 结构 T 细胞依赖性双特异性抗体的平台，这种抗体对肿瘤细胞上的 HER2 受体具有双价性，对 T 细胞上的 CD3 受体具有单价性。为此，我们在基因编码的酪氨酸残基上使用了生物反电子需求狄尔斯-阿尔德（IEDDA）点击反应，在已获批准用于治疗的抗体曲妥珠单抗上安装了一个 TCO 手柄。随后，TCO-四嗪与四嗪功能化的 CD3 结合 Fab 发生点击反应，产生了 2:1 HER2 × CD3 TDBA，在皮摩尔浓度下具有杀灭肿瘤的能力。对 T 细胞 CD3 受体的单价性可以降低细胞因子释放综合征的发生几率，而细胞因子释放综合征是此类制剂的常见副作用。我们的半合成方法只需几个化学酶和合成步骤就能生成高效的 TDBA 构建体。
{"title":"Modular Semisynthetic Approach to Generate T Cell-Dependent Bispecific Constructs from Recombinant IgG1 Antibodies","authors":"Irene Shajan, Léa N. C. Rochet, Shannon R. Tracey, Rania Benazza, Bianka Jackowska, Oscar Hernandez-Alba, Sarah Cianférani, Christopher J. Scott, Floris L. van Delft, Vijay Chudasama, Bauke Albada","doi":"10.1021/acs.bioconjchem.4c00309","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00309","url":null,"abstract":"Redirecting T cells to tumor cells by bispecific antibodies is an effective approach to treat cancer, and T cell-dependent bispecific antibodies (TDBAs) are an emerging class of potent immunotherapeutic agents. By simultaneously targeting antigens on tumor cells and T cells, T cells are activated to kill tumor cells. Herein, we report a platform to generate a novel class of 2:1 structure of T cell-dependent bispecific antibody with bivalency for HER2 receptors on tumor cells and monovalency for CD3 receptors on T cells. For this, we use a biogenic inverse electron-demand Diels–Alder (IEDDA) click reaction on genetically encoded tyrosine residues to install one TCO handle on therapeutically approved antibody trastuzumab. Subsequent TCO-tetrazine click with a tetrazine-functionalized CD3-binding Fab yields a 2:1 HER2 × CD3 TDBA that exhibits a tumor-killing capability at picomolar concentrations. Monovalency toward the CD3 receptor on T cells can lower the chances of cytokine release syndrome, which is a common side effect of such agents. Our semisynthetic approach can generate highly potent TDBA constructs in a few chemoenzymatic and synthetic steps.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1021/acs.bioconjchem.4c00336
Anna L. Malinowska, Harley L. Huynh, Andrés F. Correa-Sánchez, Sritama Bose
Chemical conjugation of oligonucleotides is widely used to improve their delivery and therapeutic potential. A variety of strategies are implemented to efficiently modify oligonucleotides with conjugating partners. The linkers typically used for oligonucleotide conjugation have limitations in terms of stability or ease of synthesis, which generates the need for providing new improved linkers for oligonucleotide conjugation. Herein, we report the synthesis of novel vinylpyrimidine phosphoramidite building blocks, which can be incorporated into an oligonucleotide by standard solid-phase synthesis in an automated synthesizer. These linker-bearing oligonucleotides can be easily conjugated in a biocompatible manner with thiol-functionalized molecules leading to the efficient generation of oligonucleotide conjugates.
{"title":"Thiol-Specific Linkers for the Synthesis of Oligonucleotide Conjugates via Metal-Free Thiol–Ene Click Reaction","authors":"Anna L. Malinowska, Harley L. Huynh, Andrés F. Correa-Sánchez, Sritama Bose","doi":"10.1021/acs.bioconjchem.4c00336","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00336","url":null,"abstract":"Chemical conjugation of oligonucleotides is widely used to improve their delivery and therapeutic potential. A variety of strategies are implemented to efficiently modify oligonucleotides with conjugating partners. The linkers typically used for oligonucleotide conjugation have limitations in terms of stability or ease of synthesis, which generates the need for providing new improved linkers for oligonucleotide conjugation. Herein, we report the synthesis of novel vinylpyrimidine phosphoramidite building blocks, which can be incorporated into an oligonucleotide by standard solid-phase synthesis in an automated synthesizer. These linker-bearing oligonucleotides can be easily conjugated in a biocompatible manner with thiol-functionalized molecules leading to the efficient generation of oligonucleotide conjugates.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1021/acs.bioconjchem.4c00275
Bayan Alkhawaja, Duaa Abuarqoub, Mohammad Al-natour, Walhan Alshaer, Qasem Abdallah, Ezaldeen Esawi, Malak Jaber, Nour Alkhawaja, Bayan Y. Ghanim, Nidal Qinna, Andrew G. Watts
Adopting conventional conjugation approaches to construct antibody-targeted nanoparticles (NPs) has demonstrated suboptimal control over the binding orientation and the structural stability of monoclonal antibodies (mAbs). Hitherto, the developed antibody-targeted NPs have shown proof of concept but lack product homogeneity, batch-to-batch reproducibility, and stability, precluding their advancement toward the clinic. To circumvent these limitations and advance toward clinical application, herein, a refined approach based on site-specific construction of mAb-immobilized NPs will be appraised. Initially, the conjugation of atezolizumab (anti-PDL1 antibody, Amab) with polymeric NPs was developed using bis-haloacetamide (BisHalide) rebridging chemistry, followed by click chemistry (NP-Fab BisHalide Ab and NP-Fc BisHalide Ab). For comparison purposes, mAb-immobilized NPs developed utilizing conventional conjugation methods, namely, N-hydroxysuccinimide (NHS) coupling and maleimide chemistry (NP-NHS Ab and NP-Mal Ab), were included. Next, flow cytometry and confocal microscopy experiments evaluated the actively targeted NPs (loaded with fluorescent dye) for cellular binding and uptake. Our results demonstrated the superior and selective binding and uptake of NP-Fab BisHalide Ab and NP-Fc BisHalide Ab into EMT6 cells by 19-fold and 13-fold, respectively. To evaluate the PDL1-dependent cell uptake and the selectivity of the treatments, a blocking step of the PDL1 receptor with Amab was performed prior to incubation with NP-Fab BisHalide Ab and NP-Fc BisHalide Ab. To our delight, the binding and uptake of fluorescent NPs were reduced significantly by 3-fold for NP-Fab BisHalide Ab, demonstrating the PDL1-mediated uptake. Moreover, NP-Fab BisHalide Ab and NP-Fc BisHalide Ab were entrapped with the paclitaxel payload, and their cytotoxicity was evaluated. They showed significant enhancements compared to free paclitaxel and NP-NHS Ab. Overall, this work will provide a facile conjugation method that could be implemented to actively target NPs with a plethora of therapeutic mAbs approved for various malignancies.
采用传统的共轭方法构建抗体靶向纳米粒子（NPs）对单克隆抗体（mAbs）的结合方向和结构稳定性的控制并不理想。迄今为止，已开发出的抗体靶向 NPs 已证明了概念，但缺乏产品同质性、批次间的可重复性和稳定性，因此无法将其推向临床。为了规避这些限制并推进临床应用，本文将评估一种基于特定位点构建 mAb 固定化 NPs 的改进方法。起初，我们使用双卤乙酰胺（BisHalide）再桥接化学方法开发了atezolizumab（抗 PDL1 抗体，Amab）与聚合物 NPs 的共轭，然后使用点击化学方法（NP-Fab BisHalide Ab 和 NP-Fc BisHalide Ab）。为便于比较，还包括利用传统连接方法，即 N-羟基琥珀酰亚胺（NHS）偶联和马来酰亚胺化学（NP-NHS Ab 和 NP-Mal Ab）开发的 mAb 固定化 NP。接着，流式细胞术和共聚焦显微镜实验评估了主动靶向 NPs（负载荧光染料）与细胞的结合和吸收情况。结果表明，NP-Fab BisHalide Ab 和 NP-Fc BisHalide Ab 与 EMT6 细胞的结合率和吸收率分别提高了 19 倍和 13 倍。为了评估 PDL1 依赖性细胞摄取和处理的选择性，在与 NP-Fab BisHalide Ab 和 NP-Fc BisHalide Ab 培养之前，先用 Amab 对 PDL1 受体进行了阻断。令我们欣喜的是，NP-Fab BisHalide Ab 与荧光 NPs 的结合和吸收显著减少了 3 倍，证明了 PDL1 介导的吸收。此外，NP-Fab BisHalide Ab 和 NP-Fc BisHalide Ab 被紫杉醇有效载荷包裹，并评估了它们的细胞毒性。与游离紫杉醇和 NP-NHS Ab 相比，它们的细胞毒性明显增强。总之，这项工作将提供一种简便的共轭方法，可用于将大量获准用于各种恶性肿瘤的治疗用 mAbs 积极靶向 NPs。
{"title":"Facile Rebridging Conjugation Approach to Attain Monoclonal Antibody-Targeted Nanoparticles with Enhanced Antigen Binding and Payload Delivery","authors":"Bayan Alkhawaja, Duaa Abuarqoub, Mohammad Al-natour, Walhan Alshaer, Qasem Abdallah, Ezaldeen Esawi, Malak Jaber, Nour Alkhawaja, Bayan Y. Ghanim, Nidal Qinna, Andrew G. Watts","doi":"10.1021/acs.bioconjchem.4c00275","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00275","url":null,"abstract":"Adopting conventional conjugation approaches to construct antibody-targeted nanoparticles (NPs) has demonstrated suboptimal control over the binding orientation and the structural stability of monoclonal antibodies (mAbs). Hitherto, the developed antibody-targeted NPs have shown proof of concept but lack product homogeneity, batch-to-batch reproducibility, and stability, precluding their advancement toward the clinic. To circumvent these limitations and advance toward clinical application, herein, a refined approach based on site-specific construction of mAb-immobilized NPs will be appraised. Initially, the conjugation of atezolizumab (anti-PDL1 antibody, Amab) with polymeric NPs was developed using bis-haloacetamide (BisHalide) rebridging chemistry, followed by click chemistry (NP-Fab BisHalide Ab and NP-Fc BisHalide Ab). For comparison purposes, mAb-immobilized NPs developed utilizing conventional conjugation methods, namely, <i>N</i>-hydroxysuccinimide (NHS) coupling and maleimide chemistry (NP-NHS Ab and NP-Mal Ab), were included. Next, flow cytometry and confocal microscopy experiments evaluated the actively targeted NPs (loaded with fluorescent dye) for cellular binding and uptake. Our results demonstrated the superior and selective binding and uptake of NP-Fab BisHalide Ab and NP-Fc BisHalide Ab into EMT6 cells by 19-fold and 13-fold, respectively. To evaluate the PDL1-dependent cell uptake and the selectivity of the treatments, a blocking step of the PDL1 receptor with Amab was performed prior to incubation with NP-Fab BisHalide Ab and NP-Fc BisHalide Ab. To our delight, the binding and uptake of fluorescent NPs were reduced significantly by 3-fold for NP-Fab BisHalide Ab, demonstrating the PDL1-mediated uptake. Moreover, NP-Fab BisHalide Ab and NP-Fc BisHalide Ab were entrapped with the paclitaxel payload, and their cytotoxicity was evaluated. They showed significant enhancements compared to free paclitaxel and NP-NHS Ab. Overall, this work will provide a facile conjugation method that could be implemented to actively target NPs with a plethora of therapeutic mAbs approved for various malignancies.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"234 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1021/acs.bioconjchem.4c00337
Jeremy M. Quintana, Jonathan C. T. Carlson, Ella Scott, Thomas S. C. Ng, Miles A. Miller, Ralph Weissleder
Positron emission tomography (PET) imaging methods have advanced our understanding of human biology, while targeted radiotherapeutic drug treatments are now routinely used clinically. The field is expected to grow considerably based on an expanding repertoire of available affinity ligands, radionuclides, conjugation chemistries, and their FDA approvals. With this increasing use, strategies for dose reduction have become of high interest to protect patients from unnecessary and off-target toxicity. Here, we describe a simple and powerful method, scission-enhanced molecular imaging (SEMI). The technique allows for rapid corporeal elimination of radionuclides once imaging or theranostic treatment is completed and relies on “click-to-release” bioorthogonal linkers.
{"title":"Scission-Enhanced Molecular Imaging (SEMI)","authors":"Jeremy M. Quintana, Jonathan C. T. Carlson, Ella Scott, Thomas S. C. Ng, Miles A. Miller, Ralph Weissleder","doi":"10.1021/acs.bioconjchem.4c00337","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00337","url":null,"abstract":"Positron emission tomography (PET) imaging methods have advanced our understanding of human biology, while targeted radiotherapeutic drug treatments are now routinely used clinically. The field is expected to grow considerably based on an expanding repertoire of available affinity ligands, radionuclides, conjugation chemistries, and their FDA approvals. With this increasing use, strategies for dose reduction have become of high interest to protect patients from unnecessary and off-target toxicity. Here, we describe a simple and powerful method, scission-enhanced molecular imaging (SEMI). The technique allows for rapid corporeal elimination of radionuclides once imaging or theranostic treatment is completed and relies on “click-to-release” bioorthogonal linkers.","PeriodicalId":501658,"journal":{"name":"Bioconjugate Chemistry","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：