Bioconjugate Chemistry最新文献

{"title":"Innovative Glucagon-like Peptide 1 Receptor Agonists: Exploring the Therapeutic Potential of Specific Modified Monomer, Dimer, and Tetramer in Type 2 Diabetes Treatment.","authors":"Yan Du, Tao Liu, Hua-Lin Li, Qun Luo, Xiao-Yuan Guo, Jian-Yun Wang, Xin-Rui Wang, Ya-Man Zhou, Ya-Wen Pan, Li-Cheng Yu, Hong-Mei Tan, Ke-Sheng Hu, Song-Shan Tang","doi":"10.1021/acs.bioconjchem.5c00261","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00261","url":null,"abstract":"<p><p>Modified glucagon-like peptide 1 (GLP-1) plays a crucial role in type 2 diabetes (T2D) treatment. The comparative hypoglycemic effect among fatty-acid-modified GLP-1 monomer G20, dimer 2G21, and tetramer 4G18 was evaluated in T2D mice. The polymers exhibited an opposite solubility with their monomers. After single administration, the oral glucose tolerance test results showed that the monomers, dimer, or tetramer, respectively, had 3-9, 21, or 35 days of hypoglycemic effect or plasma stability. G20 had a moderate hypoglycemic effect, and its peak effect occurred in week 1 as semaglutide. 2G21 showed a strongly hypoglycemic effect in week 1-10, and its peak effect occurred in week 4. 4G18 had a weak effect initially but rapidly strengthened in weeks 6-10 and reached its peak effect in week 10. After the 10 week interference, compared to the model control group, G20 (-19.7 or -4.3%), 2G21-L/M/H (-15.9/-34.3/-26.7% or -6.0/-34.4/-36.2%), and 4G18-L/M/H groups (-44.3/-49.8/-53.8% or -40.9/-50.6/-50.8%) significantly exhibited hypoglycemic effects in postprandial glucose or fasting plasma glucose changes. Insulin altered +4.1% (G20), -9.6/+10.0/+36.5% (2G21-L/M/H), and +38.5/+28.7/+84.8% (4G18-L/M/H). HbA_1c or body weight reduced -11.9 or -0.18% (G20), -5.2/-15.2/-19.1% or +0.5/-4.7/-1.2% (2G21-L/M/H), and -5.8/-4.8/-5.4% or -2.9/-2.1/-3.1% (4G18-L/M/H), showing a dose-dependent reduction in 2G21, whereas the 4G18 had lower variations. 2G21 induced a hypoglycemic effect and diet stress, whereas 4G18 only did a hypoglycemic effect and showed a stronger protection to the model organs and more improvement in the nerve muscle than G20 or 2G21. The endogenous insulin release depends not only on the GLP-1 peptide dose but also on the peptide chain in the polymer skeleton.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657848","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}

{"title":"Exploring Metal-Free Click Reactions: New Frontiers in Glycochemistry and Bioconjugation.","authors":"Pedro Ramírez-López, José Ramón Suárez, Aida Flores, María J Hernáiz","doi":"10.1021/acs.bioconjchem.5c00049","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00049","url":null,"abstract":"<p><p>Efficient and biocompatible methods for synthesizing glycoconjugates are essential in chemical biology, as these molecules play pivotal roles in cellular recognition, signaling, and immune responses. Abnormal glycosylation is associated with diseases such as cancer, infections, and immune disorders, positioning glycoconjugates as promising candidates for therapeutic, diagnostic, and drug delivery applications. Traditional chemical approaches often lack biocompatibility and efficiency; however, the advent of metal-free click chemistry has revolutionized glycoconjugate synthesis by providing selective and versatile tools under mild conditions. This review highlights four remarkable metal-free click reactions: thiol-ene coupling (TEC), strain-promoted azide-alkyne cycloaddition (SPAAC), inverse electron-demand Diels-Alder (IEDDA) reaction, and sulfur fluoride exchange (SuFEx). TEC enables the regio- and stereoselective synthesis of glycoconjugates, including S-polysaccharides, glycopeptides, and glycoclusters, advancing vaccine development and carbohydrate-based therapeutics. SPAAC, a bioorthogonal and metal-free alternative, facilitates <i>in vivo</i> imaging, glycan monitoring, the synthesis of glycofullerenes and glycovaccines, and the development of targeted protein degradation systems such as lysosome-targeting chimeras (LYTACs). Additionally, the combination of SPAAC with biocatalysis offers a sustainable approach for preparing glycoconjugates with therapeutic potential. The IEDDA reaction, a highly efficient metal-free biorthogonal cycloaddition, plays a key role in metabolic glycoengineering for live-cell imaging and glycan-based therapies and also contributes to the creation of injectable hydrogels for drug delivery and tissue engineering. SuFEx, a more recent reaction, enables efficient sulfonamide and sulfonate bond formation, broadening the toolbox for glycoconjugate and protein functionalization. These methodologies are transforming glycochemistry and glycobiology, driving advancements in biomedicine, materials science, and pharmaceutical development.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647968","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}

{"title":"Enzymatic Cellular Nanoparticles Deliver Payloads across Mucosal Barriers.","authors":"Luke J Kubiatowicz, Nima N Pourafzal, Nishta Krishnan, Lin Bao, Animesh Mohapatra, Weiwei Gao, Ronnie H Fang, Liangfang Zhang","doi":"10.1021/acs.bioconjchem.5c00262","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00262","url":null,"abstract":"<p><p>Patient preferred routes of administration for therapeutics and prophylactics, such as via oral delivery and inhalation, require penetration through mucosal barriers to achieve effective bioavailability. The mucus layer is composed of glycosylated mucin proteins and serves as a robust natural defense against pathogens but also significantly impedes the delivery of medicinal agents. To overcome this barrier, we developed an innovative virus-mimicking enzymatic cellular nanoparticle designed to enhance mucopenetration. Inspired by the influenza A virus, we genetically engineered the neuraminidase protein onto the surface of mammalian cell membrane, which was subsequently used to coat mRNA-loaded lipid nanoparticle cores. This enabled the resulting nanoparticles to cleave sialic acid residues within the mucus matrix, thereby facilitating mucopenetration. In vitro studies demonstrated that these enzyme-coated cellular nanoparticles effectively traversed an artificial mucus layer, significantly enhancing mRNA delivery to underlying epithelial cells. Furthermore, in vivo experiments in a murine model showed improved lung expression of the mRNA payload after intratracheal administration. By harnessing the power of viral biomimicry, this work unveils exciting possibilities for overcoming mucosal barriers.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657847","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}

{"title":"Influence of the Saccharide Structure on Cargo Loading, Thermal Properties, and Lectin Binding of Amphiphilic Glycopolymer-Polylactic Acid Block Copolymer Nanoparticles.","authors":"Kevin A Green, Anuja S Kulkarni, Penelope E Jankoski, Rachel M Worden, Bayleigh M Loving, Blaine Derbigny, Tristan D Clemons, Davita L Watkins, Sarah E Morgan","doi":"10.1021/acs.bioconjchem.5c00217","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00217","url":null,"abstract":"<p><p>Stereospecific arrangements of saccharide molecules control biological recognition and binding with proteins. These properties can also be utilized in the design of biomaterials for applications such as polymeric drug delivery, where saccharides may enhance the ability to target specific cells. Glycopolymer block copolymers incorporating pendant saccharides at high concentration have potential for use in applications; however, there is a need for further evaluation of their structure-property relationships. Accordingly, noncytotoxic amphiphilic, hybrid block copolymers (HBCs), synthesized by coupling branched polylactic acid (PLA) with linear polyacrylamides containing hydroxyethyl, β-d-glucose, or β-d-galactose moieties, were studied to determine the influence of the stereochemistry and structure of the pendant saccharide on nanoparticle formation, cargo loading, and lectin binding properties. HBCs were prepared at a target 50:50 PLA/hydrophilic block content; all compositions yielded similar spherical nanoparticle morphologies with comparable diameters on nanoprecipitation. Thermal properties and hydrophilic dye loading levels, however, were dependent on the pendant saccharide structure, attributed to differences in intramolecular interactions in the glycopolymer blocks. These findings demonstrate the importance of understanding the structure-dependent behavior for designing HBC-based therapies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647969","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}

{"title":"TfR1-Binding Peptide Conjugation Facilitates Robust and Specific siRNA Delivery to the Central Nervous System.","authors":"Tiancheng Fu, Fushun Fan, Yingying Lin, Zhenxian Mo, Minhua Zhou, Xiaolan Ye, Xiong Cai, Zaijun Zhang, Changgeng Qian, Xinjian Liu","doi":"10.1021/acs.bioconjchem.5c00225","DOIUrl":"10.1021/acs.bioconjchem.5c00225","url":null,"abstract":"<p><p>Transferrin receptor 1 (TfR1) is a ubiquitously expressed receptor characterized by rapid internalization kinetics and efficient receptor recycling, making it an attractive target for drug delivery. Herein, we investigated the potential of TfR1-binding peptide-siRNA conjugates for central nervous system (CNS)-specific gene silencing. A panel of TfR1-binding peptides and conjugation linkers were synthesized to enable siRNA attachment and evaluate their gene-silencing effects. Conjugation with the hTfR No. 894 peptide achieved effective siRNA delivery both <i>in vitro</i> and <i>in vivo</i>. Compared to ribose 2'-<i>O</i>-hexadecyl (C16)-siRNA conjugates, the hTfR No. 894-siRNA conjugation (<b>POC2</b>) elicited favorable pharmacokinetic characteristics and robust and durable silencing of the target gene across CNS regions following local administration, with minimal impact on peripheral tissues. These findings support TfR1-binding peptide conjugation as a promising strategy for CNS-targeted siRNA delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1377-1383"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339690","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}

{"title":"Addition of Oligoarginine to a Membrane Permeabilizing Peptide M-Lycotoxin Facilitates Intracellular Antibody Infusion from Microcondensate.","authors":"Junya Michibata, Yoshimasa Kawaguchi, Yusei Furuyama, Yoshihiro Sasaki, Kazunari Akiyoshi, Shiroh Futaki","doi":"10.1021/acs.bioconjchem.5c00176","DOIUrl":"10.1021/acs.bioconjchem.5c00176","url":null,"abstract":"<p><p>Coacervate-based intracellular delivery of biomacromolecules has attracted our attention due to the feasibility of easy condensation of the biomacromolecules and their controllable release. Our laboratory has developed a unique, coacervate-based delivery system that uses the conjugate of the polysaccharide pullulan with membrane-permeabilizing peptides, including L17E and M-lycotoxin. This system enables immunoglobulin G (IgG) antibodies labeled with the negatively charged fluorophore Alexa Fluor 488 to enter the cytosol directly through the plasma membrane. Cyotosolic IgG distribution is complete within a few minutes after infusion initiation, and infusion can be achieved in serum-containing medium. The purpose of this study was to refine this system to reduce the amount of antibody required while maintaining satisfactory delivery efficiencies. Therefore, pullulan conjugates with M-lytocoxin bearing two to eight arginine residues were designed to enhance the interaction of M-lycotoxin with the cell membrane. The conjugates were able to form microcondensates with Alexa Fluor 488 labeled IgGs. The addition of arginine residues improved the efficiency of cytosolic infusion and successfully reduced the amounts of both antibodies and pullulan-peptide conjugates required for the delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1494-1503"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537396","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}

{"title":"Targeting GPX4-Dependent Ferroptosis via a Dihydroartemisinin-Conjugated Cross-Linked Lipoic Acid Nanodrug for Endometrial Carcinoma Therapy.","authors":"Qi Cao, Xiao Wu, Juan Tan, Hanying Xu, Ying Zhang, Yang Hu, Yuxi Chen, Shiyong Zhang, Tian Tang","doi":"10.1021/acs.bioconjchem.5c00256","DOIUrl":"10.1021/acs.bioconjchem.5c00256","url":null,"abstract":"<p><p>Endometrial cancer (EC) is a significant global cause of cancer-related mortality. Chemoresistance is a major challenge in treating advanced or recurrent EC, necessitating the search for new anti-EC drugs. Dihydroartemisinin (DHA)-induced ferroptosis shows promise as a therapy for EC, but its poor solubility and insufficient antitumor potency hinder its clinical use. A novel nanodrug delivery system, DHA@cLAVs, was developed using cross-linked lipoic acid to enhance DHA solubility and antitumor efficacy. Benefiting from the pro-oxidant effects of lipoic acid on tumor cells and its improved water solubility, DHA@cLAVs outperformed DHA alone, showing promising ferroptosis-based antitumor effects via the c-jun/c-fos-GPX4 pathway in both in vitro and in vivo experiments, offering promising prospects for endometrial carcinoma treatment.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1541-1552"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558423","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}

{"title":"","authors":"Haonan Chen,&nbsp;Yuhang Dong*,&nbsp;Feng Shi* and Feng Li*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631025","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}

{"title":"","authors":"Jason Ren Wu,&nbsp;Akash Canjels,&nbsp;Rei Miyauchi and Ester J. Kwon*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631037","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}

{"title":"","authors":"Michael J. Capperauld,&nbsp;Krish Kiran Valluru,&nbsp;Jagandeep S. Saraya,&nbsp;Evan Zakaria,&nbsp;Connor E. Wong and Derek K. O’Flaherty*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631039","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}