Bioconjugate Chemistry最新文献_第5页

Peptide Nucleic Acid Probes for Pretargeted Affibody-Mediated Delivery of Cytotoxic Payloads to HER2-Positive Carcinoma 肽核酸探针对her2阳性癌细胞毒性载体的预先靶向修饰介导递送

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-30 DOI: 10.1021/acs.bioconjchem.6c00035

Jacob Clinton, Kristina Westerlund, Astrid Haraldsson, Ebba Nordén, Tilde Hagelin, Eleftherios Papalanis, Moeen Ud-din, Anzhelika Vorobyeva, Torbjörn Gräslund, Amelie Eriksson Karlström, Maryam Oroujeni

{"title":"Peptide Nucleic Acid Probes for Pretargeted Affibody-Mediated Delivery of Cytotoxic Payloads to HER2-Positive Carcinoma","authors":"Jacob Clinton, Kristina Westerlund, Astrid Haraldsson, Ebba Nordén, Tilde Hagelin, Eleftherios Papalanis, Moeen Ud-din, Anzhelika Vorobyeva, Torbjörn Gräslund, Amelie Eriksson Karlström, Maryam Oroujeni","doi":"10.1021/acs.bioconjchem.6c00035","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.6c00035","url":null,"abstract":"This study investigates how the structural design ofsecondaryPNA probes affects their ability to carry the cytotoxic agent DM1in a novel affibody-PNA-based pretargeting approach directed at HumanEpidermal growth factor Receptor 2 (HER2)-expressing cells. Six differentDM1-conjugated secondary 8-mer PNA probes with strategic hydrophilicmodifications were designed and evaluated. Surface plasmon resonanceanalysis confirmed that the modifications preserved hybridizationto the HER2-targeting affibody-PNA primary probe, with all secondaryprobes showing similar binding kinetics (KD = 310–660 pM). Biodistribution studies in nontumor-bearingNMRI mice with lutetium-177 (177Lu)-labeled secondary probesrevealed that probe modifications dramatically influenced organ distributionpatterns. The secondary probes SP2, SP5, and SPc demonstrated favorablebiodistribution profiles with reduced accumulation in critical organs,i.e., liver and kidneys. Receptor-mediated endocytosis was also affectedby secondary probe design, showing an increase in cellular internalizationfor SP5 (20.4% after 24 h) compared to SP2 (12.1%). Our findings highlighthow rational design can optimize in vivo pharmacokinetics while preservingbinding properties essential for effective pretargeting, providinga foundation for developing novel targeted cytotoxic delivery systemswith potentially improved therapeutic indexes.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1562–1570"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769789","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

Discovery of a Novel Tripeptide Linker that Broadens the Therapeutic Window of Auristatin-Based Antibody–Drug Conjugates by Reducing Bone Marrow Toxicity 一种新型三肽连接物的发现，通过降低骨髓毒性，拓宽了基于耳听觉素的抗体-药物偶联物的治疗窗口。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-23 DOI: 10.1021/acs.bioconjchem.6c00234

Noah A. Bindman, Forgivemore Magunda, Vineet Kumar, Niels V. Rekers, David J. Ortiz, Esther S. Trueblood, Scott Blackburn, Roma Yumul, Divya Awasthi, Katie Caspary, Lauren Farr, Calvin Neace, Sarah Anderson, Brendan Drouhard, Xinqun Zhang, Hector Rincon-Arano, Matthew R. Levengood, Nicole M. Okeley, Peter D. Senter

{"title":"Discovery of a Novel Tripeptide Linker that Broadens the Therapeutic Window of Auristatin-Based Antibody–Drug Conjugates by Reducing Bone Marrow Toxicity","authors":"Noah A. Bindman, Forgivemore Magunda, Vineet Kumar, Niels V. Rekers, David J. Ortiz, Esther S. Trueblood, Scott Blackburn, Roma Yumul, Divya Awasthi, Katie Caspary, Lauren Farr, Calvin Neace, Sarah Anderson, Brendan Drouhard, Xinqun Zhang, Hector Rincon-Arano, Matthew R. Levengood, Nicole M. Okeley, Peter D. Senter","doi":"10.1021/acs.bioconjchem.6c00234","DOIUrl":"10.1021/acs.bioconjchem.6c00234","url":null,"abstract":"Vedotin-based antibody–drugconjugates (ADCs) employingthe valine–citrulline (Val–Cit) dipeptide linker andmonomethyl auristatin E (MMAE) have achieved substantial clinicalsuccess but are frequently limited by dose-limiting hematologic toxicities,including neutropenia. These toxicities are hypothesized to arise,in part, from extracellular cleavage of the Val–Cit linkerby neutrophil-derived proteases within the bone marrow microenvironment.Here, we describe the discovery and characterization of a tumor-selectivetripeptide linker that improves the therapeutic index of MMAE-basedADCs. Using a high-throughput fluorescent peptide library screenedagainst cancer and bone marrow homogenates, we identified peptidemotifs preferentially cleaved in cancer lysates. Incorporation ofthese motifs into MMAE-containing drug linkers revealed a D-amino-acid–containing tripeptide (DLeu-Ala-Glu) that retainedintracellular potency while exhibiting reduced susceptibility to neutrophilelastase and proteinase 3. ADCs bearing this linker demonstrated markedlyreduced bone marrow toxicity in rats and cynomolgus monkeys relativeto vedotin controls, with improved tolerability at higher doses andpreserved antitumor efficacy across multiple xenograft models. Mechanisticstudies showed that reduced linker proteolysis and increased linkerhydrophilicity both contributed to reduced toxicity relative to vedotin.Together, these data demonstrate that rational peptide linker designintegrating protease selectivity and physicochemical properties cansubstantially improve the safety profile of MMAE-based ADCs withoutcompromising efficacy.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1643–1656"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560130","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

Next-Generation Glycan Materials Bridging Organic and Inorganic Chemistry 连接有机与无机化学的新一代聚糖材料

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-30 DOI: 10.1021/acs.bioconjchem.6c00321

Matthew M. Campbell, Jorge A. Carmona, Charlotte E. Hantus, Anna K. Keum, Rohan Pillai, Sarah K. Vest, Julia M. Stauber

{"title":"Next-Generation Glycan Materials Bridging Organic and Inorganic Chemistry","authors":"Matthew M. Campbell, Jorge A. Carmona, Charlotte E. Hantus, Anna K. Keum, Rohan Pillai, Sarah K. Vest, Julia M. Stauber","doi":"10.1021/acs.bioconjchem.6c00321","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.6c00321","url":null,"abstract":"The central roles that glycans play in cell communication,adhesion,signal transduction, and pathogen recognition have driven growinginterest in understanding glycan-mediated protein recognition events.Because protein–glycan binding is governed by three-dimensionalcarbohydrate presentation, precise structural control over syntheticglycan assemblies is essential for understanding fundamental principlesunderlying the recognition of both natural and artificial glycans.Most conventional glycomimetics, however, often lack the precise structuralorganization characteristic of native glycans, which limits detailedunderstanding of the architectural parameters that dictate their function.Molecular inorganic glycan assemblies provide an emerging platformthat provides control over glycan valency, spacing, and topology toachieve programmable recognition behavior. This Viewpoint highlightsthe development of metal-templated glycan complexes that afford well-definedarchitectures with tunable recognition behavior and biological functionand also discusses developing opportunities at the interface of inorganicand organic chemistry, glycobiology, and biomolecular design.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1523–1529"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769812","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

Transport of Engineered Nanoparticles in Solid Tumors: Mechanistic Barriers and Emerging Delivery Strategies 工程纳米颗粒在实体肿瘤中的运输：机械障碍和新兴的递送策略。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-06-26 DOI: 10.1021/acs.bioconjchem.6c00162

Ananya Singh, Navneet Kaur, Nimeet Desai, Ankush Ankush, Lalit Prashant Meena, Kanchan Chauhan, Lalitkumar K. Vora, Rajendra Prasad

{"title":"Transport of Engineered Nanoparticles in Solid Tumors: Mechanistic Barriers and Emerging Delivery Strategies","authors":"Ananya Singh, Navneet Kaur, Nimeet Desai, Ankush Ankush, Lalit Prashant Meena, Kanchan Chauhan, Lalitkumar K. Vora, Rajendra Prasad","doi":"10.1021/acs.bioconjchem.6c00162","DOIUrl":"10.1021/acs.bioconjchem.6c00162","url":null,"abstract":"Uponsystemic injection, targeted delivery and site-specific tumoraccumulation of nanoparticle-based medicines are major challenges.Moreover, their complex design, batch-to-batch variability, particlesize heterogeneity, and surface charge variation alter the targetingand biodistribution of injected nanomedicines. We have reviewed howtumor complexity profoundly affects nanoparticles’ tumor transport,penetration, and retention. In this article, the enhanced permeabilityand retention (EPR) mechanism and active transport and retention (ATR)principles defining nanoparticles’ tumor accumulation havebeen discussed. Enhanced permeability and retention support nanoparticles’passive entry into the tumor through endothelial cell gaps, whereasactive transport and retention allow nanoparticles’ entry throughactive endothelial transport processes. Critical issues of tumor barriersand stimulus-responsive approaches for enhanced tumor delivery ofnanoparticles have also been discussed. By integrating the major deliverybottlenecks with evolving alternative solutions, this review providesa framework to support rational nanocarrier design and their emergingtumor delivery strategies.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1495–1506"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325157","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

Tumor-Responsive Delivery of 5-Fluorouracil from a Redox-Triggered Supramolecular Gelator 氧化还原触发的超分子凝胶对5-氟尿嘧啶的肿瘤反应性递送

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-08-10 DOI: 10.1021/acs.bioconjchem.6c00108

Marko Mihajlovic, Milos Mihajlovic, Paola Alletto, Slavko Kralj, Natalia Rosso, Silvia Marchesan

{"title":"Tumor-Responsive Delivery of 5-Fluorouracil from a Redox-Triggered Supramolecular Gelator","authors":"Marko Mihajlovic, Milos Mihajlovic, Paola Alletto, Slavko Kralj, Natalia Rosso, Silvia Marchesan","doi":"10.1021/acs.bioconjchem.6c00108","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.6c00108","url":null,"abstract":"5-Fluorouracil (5-FU)is a chemotherapeutic drug that is widelyused to treat gastrointestinal cancers (e.g., hepatocellular carcinoma).Unfortunately, its systemic toxicity limits its clinical utility;therefore, new means for its targeted delivery at the pathologicalsite are highly sought after to enhance therapeutic efficacy. In thiswork, we describe a 5-FU covalent conjugate with the self-assembling,heterochiral tripeptide DLeu-Phe-Phe (lFF) via a redox-sensitivelinker (5-FU-SS-lFF). The conjugate yields supramolecular hydrogelswith rheological properties similar to those of lFF hydrogels andenables 5-FU release under reducing conditions, such as those presentin the tumor microenvironment. We demonstrate the selectivity of thedrug release under such conditions over a period of 24 h, with consequentsignificant cytotoxicity on cancer cells, as demonstrated on hepatocellularcarcinoma spheroids. Overall, this study opens new opportunities forpeptide-based supramolecular hydrogels as versatile and smart vehiclesfor the selective release of anticancer drugs under tumor-like reducingconditions.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1571–1581"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769713","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

Receptor-Targeted Folic Acid Ligand–Drug Conjugate of Exatecan Leads to Complete Tumor Regression in the Preclinical Tumor Model 受体靶向叶酸配体-艾替替康药物偶联物在临床前肿瘤模型中导致肿瘤完全消退。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-14 DOI: 10.1021/acs.bioconjchem.6c00330

Dhanashree Murugan, Loganathan Rangasamy

{"title":"Receptor-Targeted Folic Acid Ligand–Drug Conjugate of Exatecan Leads to Complete Tumor Regression in the Preclinical Tumor Model","authors":"Dhanashree Murugan, Loganathan Rangasamy","doi":"10.1021/acs.bioconjchem.6c00330","DOIUrl":"10.1021/acs.bioconjchem.6c00330","url":null,"abstract":"Thefolate receptors (FR) are highly overexpressed invarious solidtumors and metastatic cancers, whereas they are low or negligiblein healthy cells. This provides a window of opportunity to deliverany payload by specifically targeting these receptors. This studydevelops a delivery strategy for exatecan (payload), a Top1 inhibitor,via the Fol-SS-Exa (8) conjugate, demonstrating its potencyagainst FR-positive cancer cells in vitro and in preclinical studies.The design of the Fol-SS-Exa (8) conjugate features folateas a ligand targeting FRα and a cleavable disulfide linker thatremains stable under physiological conditions. Exatecan (6), a highly potent cytotoxic payload, arrests cell division in cancercells. Fol-SS-Exa (8) exhibited an IC50 valueof 4.88 nM in the FR-positive MDA-MB-231 cell line. The Fol-SS-Exaconjugate (8), administered to tumor-induced C57BL/6mice, exhibited complete regression after three injections (7.5 mg/kgbody weight), highlighting its potent antitumor activity. In addition,the conjugate (8) demonstrated the ability to eradicatethe toxicity of exatecan (6) when administered alone.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1720–1730"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443483","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

Suppressive Immune Response of Poly(sarcosine) Conjugated Proteins: PSARylation 聚（肌氨酸）偶联蛋白的抑制免疫反应：PSARylation。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-15 DOI: 10.1021/acs.bioconjchem.6c00159

Noritomo Tsuda, Yota Okuno, Akari Yasuda, Mitsuru Ando, Yasuhiko Iwasaki

{"title":"Suppressive Immune Response of Poly(sarcosine) Conjugated Proteins: PSARylation","authors":"Noritomo Tsuda, Yota Okuno, Akari Yasuda, Mitsuru Ando, Yasuhiko Iwasaki","doi":"10.1021/acs.bioconjchem.6c00159","DOIUrl":"10.1021/acs.bioconjchem.6c00159","url":null,"abstract":"Polymer conjugation is a widely used strategy to improvethe pharmacokineticsof protein therapeutics by extending their half-life and protectingthem from degradation. Poly(ethylene glycol) (PEG) is the most commonlyused polymer for this purpose. However, its use can trigger unwantedimmune responses, leading to the production of anti-PEG antibodiesthat compromise efficacy. This issue has driven the search for alternativepolymers, with poly(sarcosine) (PSAR), derived from an endogenousamino acid, emerging as a promising candidate. Despite this potential,the immunogenicity of PSAR–protein conjugates (PSARylation)has not been systematically compared with that of PEGylated counterparts.In this report, we show that conjugating a model protein antigen tohigh-molecular-weight PSAR more effectively suppresses immune responsesagainst both the protein and the polymer than PEG. Although polymerconjugation has traditionally been viewed as a means of steric “masking”of a protein, our results demonstrate that the chemical nature ofthe polymer is a critical, independent factor, as PSAR conjugateselicited lower antibody production than PEG conjugates of identicalhydrodynamic size. This study highlights polymer selection as an importantdesign parameter for minimizing immunogenicity in next-generationprotein therapeutics. Polymers derived from biological building blocks,such as PSAR, offer a promising route to developing safer, more effectivebiopharmaceuticals with better tolerance and reduced risk of adverseimmune reactions.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1582–1590"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454089","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 Chemistry in Antibody–Drug Conjugates: Current Strategies, Clinical Pharmacokinetic Analyses, and Linker-Free Outlooks 抗体-药物偶联物中的连接物化学：当前策略、临床药代动力学分析和无连接物的前景。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-23 DOI: 10.1021/acs.bioconjchem.6c00299

Theeraphop Prachyathipsakul, Prachi Gupta, Seth K. Thayumanavan, Sandhya Vijay, Karuppiah Kannan, S. Thayumanavan

{"title":"Linker Chemistry in Antibody–Drug Conjugates: Current Strategies, Clinical Pharmacokinetic Analyses, and Linker-Free Outlooks","authors":"Theeraphop Prachyathipsakul, Prachi Gupta, Seth K. Thayumanavan, Sandhya Vijay, Karuppiah Kannan, S. Thayumanavan","doi":"10.1021/acs.bioconjchem.6c00299","DOIUrl":"10.1021/acs.bioconjchem.6c00299","url":null,"abstract":"Withthe increasing cancer incidence and death tolls worldwide,antibody–drug conjugates (ADCs) have emerged as a promisingplatform to selectively deliver cytotoxic payloads to cancerous tissues.This platform has the potential to spare patients from off-targeteffects compared to traditional chemotherapy. Despite the clinicalsuccess of some ADCs, many in the pipeline did not even reach theclinical stage. We turn our attention to their linker chemistry thatconnects the antibody and the drug molecules together. Despite theirsmall size, linkers play a key role in governing the payload releasekinetics and location. In this Viewpoint, we collect and discuss aplethora of linkers employed in ADC development, specifically focusingon advancements in antibody modification and linker cleavage chemistries.The choice of linker chemistry has evolved over time, going from stochasticallyattached non-stimuli-responsive to site-specifically modified cleavablelinkers. Then we correlate the linker technologies to their pharmacokineticoutcomes in clinics, followed by a discussion of the upcoming “linker-free”technology for more facile and efficient antibody-conjugated targeteddelivery.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1507–1515"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576222","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

Organometallic Chemistry Approach to Peptide Tricycles 肽三环的有机金属化学方法。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-24 DOI: 10.1021/acs.bioconjchem.6c00185

Nima Adhami, Michael J.P. Rebelo, Rebecca A. Jenkins, Eileen J. Olivares, Rachel R. Ogorzalek Loo, Songrong Qu, Melanie J. Olivares, Reanne J. Coutinho, Evan A. Doud, Tyler A. Kerr, Austin D. Ready, Yueying Wang, Brendan J. Mahoney, Robert T. Clubb, Joseph A. Loo, Jose A. Rodriguez, Alexander M. Spokoyny

{"title":"Organometallic Chemistry Approach to Peptide Tricycles","authors":"Nima Adhami, Michael J.P. Rebelo, Rebecca A. Jenkins, Eileen J. Olivares, Rachel R. Ogorzalek Loo, Songrong Qu, Melanie J. Olivares, Reanne J. Coutinho, Evan A. Doud, Tyler A. Kerr, Austin D. Ready, Yueying Wang, Brendan J. Mahoney, Robert T. Clubb, Joseph A. Loo, Jose A. Rodriguez, Alexander M. Spokoyny","doi":"10.1021/acs.bioconjchem.6c00185","DOIUrl":"10.1021/acs.bioconjchem.6c00185","url":null,"abstract":"Herein, we demonstrate how Au(III) organometallic chemistryoffersthe potential to streamline the generation of constrained peptidetricycles. By leveraging the chemoselectivity and ultrafast kineticsof tetrametallic Au(III)-based aryl reagents toward cysteine (Cys)bioconjugation, we have constructed a small library of constrainedpeptide tricycles. These tricycles can be synthesized and isolatedin 25–55% yields from various tetracysteine-containing linearpeptides. In all cases, tricyclization conversion occurs quantitativelyunder five min at sub-mM concentrations of the target peptide andproceeds under varied distributions of the four Cys residues in thetarget peptide sequence. Furthermore, by constraining various linearpeptides around the aryl core of tetraphenylethylene, a common solid-stateluminogen, we generate fluorescent macrocycles with robust solution-stateemissive profiles. We evaluated the innate affinity of these fluorescenthybrid peptides toward cells, finding that they behave as highly selectiveluminogenic cell markers of cellular debris.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1622–1632"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589194","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

Synthesis of Glycooligomers with Defined Sialyllactose Valency and Spacing for Multivalent Binding to Influenza Hemagglutinin 与流感血凝素多价结合的具有确定唾液基乳糖价和间隔的糖异构体的合成。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-08-19 Epub Date: 2026-07-16 DOI: 10.1021/acs.bioconjchem.6c00298

Yusuke Kumon, Masanori Nagao, Hikaru Matsumoto, Sotaro Tsuji, Teruhiko Matsubara, Yu Hoshino, Toshinori Sato, Yoshiko Miura

{"title":"Synthesis of Glycooligomers with Defined Sialyllactose Valency and Spacing for Multivalent Binding to Influenza Hemagglutinin","authors":"Yusuke Kumon, Masanori Nagao, Hikaru Matsumoto, Sotaro Tsuji, Teruhiko Matsubara, Yu Hoshino, Toshinori Sato, Yoshiko Miura","doi":"10.1021/acs.bioconjchem.6c00298","DOIUrl":"10.1021/acs.bioconjchem.6c00298","url":null,"abstract":"Influenza A virus is a medically important target. Hemagglutinin(HA), a trimeric glycoprotein on the viral surface, recognizes sialylatedglycans through three receptor-binding sites. Glycoligands that interactwith HA through multivalent binding can serve as viral inhibitors.To achieve efficient multivalent binding, precise control over glycoligandstructures is essential. Here, we synthesized glycooligomers displayingsialyllactose units at defined intramolecular spacings and investigatedhow ligand structure affects binding to HA. Glycooligomers displayingone, two, or three sialyllactose units at regular intervals exhibitedenhanced binding as carbohydrate valency increased. When the spacingbetween two sialyllactose units was varied, shorter spacing enhancedbinding, likely because of a statistical rebinding effect. Interestingly,the presentation of an excessive number of sialyllactose units weakenedthe interaction with HA, presumably because of steric hindrance. Thesefindings highlight the importance of precise carbohydrate arrangementin the design of effective multivalent ligands.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 8","pages":"1711–1719"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467920","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