Antibody tocolysis targeting oxytocin receptor

preprint OA: closed CC-BY-4.0
📄 Open PDF Full text JSON View at publisher

Abstract

Abstract Preterm birth, defined as delivery before 37 weeks of gestation, poses significant risks to maternal and neonatal health. These risks include neonatal respiratory distress syndrome, intraventricular hemorrhage, long-term developmental challenges, and in severe cases, mortality. Addressing these issues, G protein-coupled receptor (GPCR)-mediated tocolysis has become a focal strategy in pharmaceutical research to mitigate preterm labor risks. Most GPCR drugs are small molecules, yet their tendency to cross the placental barrier and induce fetal toxicity presents a significant challenge. Antibody drugs, with minimal cell membrane permeability, offer a promising alternative. In this study, we leveraged AI-driven protein design to enable nanobody screening and identified several nanobodies with antagonist activity against the oxytocin receptor, a key target for preterm birth therapeutics. One of these nanobodies demonstrated antagonist activity comparable to atosiban, a commonly used clinical drug, while exhibiting superior subtype selectivity. Pharmacological and structural analyses revealed mechanisms distinct from small molecule antagonists. These findings expand the pharmacological potential of antibody drugs and introduce novel tools and perspectives for developing effective tocolytic agents.
Full text 13,858 characters · extracted from preprint-html · click to expand
Antibody tocolysis targeting oxytocin receptor | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Antibody tocolysis targeting oxytocin receptor Xiangyu Liu, Jia Nie, Kaixuan Gao, Xin Zhang, Qi Li, Hengyu Meng, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6708933/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Preterm birth, defined as delivery before 37 weeks of gestation, poses significant risks to maternal and neonatal health. These risks include neonatal respiratory distress syndrome, intraventricular hemorrhage, long-term developmental challenges, and in severe cases, mortality. Addressing these issues, G protein-coupled receptor (GPCR)-mediated tocolysis has become a focal strategy in pharmaceutical research to mitigate preterm labor risks. Most GPCR drugs are small molecules, yet their tendency to cross the placental barrier and induce fetal toxicity presents a significant challenge. Antibody drugs, with minimal cell membrane permeability, offer a promising alternative. In this study, we leveraged AI-driven protein design to enable nanobody screening and identified several nanobodies with antagonist activity against the oxytocin receptor, a key target for preterm birth therapeutics. One of these nanobodies demonstrated antagonist activity comparable to atosiban, a commonly used clinical drug, while exhibiting superior subtype selectivity. Pharmacological and structural analyses revealed mechanisms distinct from small molecule antagonists. These findings expand the pharmacological potential of antibody drugs and introduce novel tools and perspectives for developing effective tocolytic agents. Biological sciences/Biological techniques/High-throughput screening Biological sciences/Biochemistry/Structural biology/Electron microscopy/Cryoelectron microscopy Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementaryinformation.pdf Supplementary Figure1-7 and Table S1-S2 RS.pdf Reporting Summary Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6708933","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":470578040,"identity":"3685adc2-2b0b-4d39-9ef7-c3a2b94cc8f4","order_by":0,"name":"Xiangyu Liu","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-3178-9238","institution":"Tsinghua University","correspondingAuthor":true,"prefix":"","firstName":"Xiangyu","middleName":"","lastName":"Liu","suffix":""},{"id":470578041,"identity":"7a7babed-749e-464c-805a-66eca3b2c5ed","order_by":1,"name":"Jia Nie","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Nie","suffix":""},{"id":470578042,"identity":"f5d84759-7cf3-4125-9c5c-d3cebb40c375","order_by":2,"name":"Kaixuan Gao","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Kaixuan","middleName":"","lastName":"Gao","suffix":""},{"id":470578043,"identity":"d5383dfe-b2ed-4b86-aed2-98096cfb04dd","order_by":3,"name":"Xin Zhang","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Zhang","suffix":""},{"id":470578044,"identity":"cadf9fef-6824-4ee1-b14b-bc8ad62c152c","order_by":4,"name":"Qi Li","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Li","suffix":""},{"id":470578045,"identity":"9c90152f-fc8f-48cd-8181-93d41727aac0","order_by":5,"name":"Hengyu Meng","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Hengyu","middleName":"","lastName":"Meng","suffix":""},{"id":470578046,"identity":"f91055c4-37ad-4a78-90ff-870809f4ad8c","order_by":6,"name":"Xiaowen Zhang","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Xiaowen","middleName":"","lastName":"Zhang","suffix":""},{"id":470578047,"identity":"ae4d5ae8-e9be-4e7c-a9f5-24bf0b19be81","order_by":7,"name":"Yanying Wu","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Yanying","middleName":"","lastName":"Wu","suffix":""},{"id":470578048,"identity":"bcf1d13f-3066-46ad-99cc-51c9df457f6c","order_by":8,"name":"Hongtao Zeng","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Hongtao","middleName":"","lastName":"Zeng","suffix":""},{"id":470578049,"identity":"f7fb24fc-d7a4-4fd1-aeaa-aed92a6a6b6a","order_by":9,"name":"Lijuan Liu","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Lijuan","middleName":"","lastName":"Liu","suffix":""},{"id":470578050,"identity":"0d04e6d7-fffb-4766-af88-4ce3be26508d","order_by":10,"name":"Xiaoou Sun","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoou","middleName":"","lastName":"Sun","suffix":""},{"id":470578051,"identity":"2e99c6fb-9a22-4791-9bc6-20fd2986af38","order_by":11,"name":"Weishe Zhang","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Weishe","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-05-20 14:47:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6708933/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6708933/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84660566,"identity":"9e5cea9e-5f0b-4369-aee9-2697ed15ff90","added_by":"auto","created_at":"2025-06-16 04:19:02","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1599415,"visible":true,"origin":"","legend":"Article File","description":"","filename":"ManuscriptNCB.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6708933/v1_covered_28e0b30d-f872-4c2d-9d37-f1ce5119bd38.pdf"},{"id":84660404,"identity":"ee189424-4d6b-49e0-b044-3f2cf7376cb6","added_by":"auto","created_at":"2025-06-16 04:10:59","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":37827841,"visible":true,"origin":"","legend":"Supplementary Figure1-7 and Table S1-S2","description":"","filename":"Supplementaryinformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6708933/v1/d2b133b84f67160a41dd633e.pdf"},{"id":84660402,"identity":"ad1d2730-cc6d-49a7-965e-939f543cd36f","added_by":"auto","created_at":"2025-06-16 04:10:58","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":210490,"visible":true,"origin":"","legend":"Reporting Summary","description":"","filename":"RS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6708933/v1/3438b06c12a26f256e55a187.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Antibody tocolysis targeting oxytocin receptor","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6708933/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6708933/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Preterm birth, defined as delivery before 37 weeks of gestation, poses significant risks to maternal and neonatal health. These risks include neonatal respiratory distress syndrome, intraventricular hemorrhage, long-term developmental challenges, and in severe cases, mortality. Addressing these issues, G protein-coupled receptor (GPCR)-mediated tocolysis has become a focal strategy in pharmaceutical research to mitigate preterm labor risks. Most GPCR drugs are small molecules, yet their tendency to cross the placental barrier and induce fetal toxicity presents a significant challenge. Antibody drugs, with minimal cell membrane permeability, offer a promising alternative. In this study, we leveraged AI-driven protein design to enable nanobody screening and identified several nanobodies with antagonist activity against the oxytocin receptor, a key target for preterm birth therapeutics. One of these nanobodies demonstrated antagonist activity comparable to atosiban, a commonly used clinical drug, while exhibiting superior subtype selectivity. Pharmacological and structural analyses revealed mechanisms distinct from small molecule antagonists. These findings expand the pharmacological potential of antibody drugs and introduce novel tools and perspectives for developing effective tocolytic agents.","manuscriptTitle":"Antibody tocolysis targeting oxytocin receptor","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-16 04:10:54","doi":"10.21203/rs.3.rs-6708933/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"69f8265d-2f98-4c73-b7dd-b4c6bac2f748","owner":[],"postedDate":"June 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":49975574,"name":"Biological sciences/Biological techniques/High-throughput screening"},{"id":49975575,"name":"Biological sciences/Biochemistry/Structural biology/Electron microscopy/Cryoelectron microscopy"}],"tags":[],"updatedAt":"2026-04-08T15:56:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-16 04:10:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6708933","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6708933","identity":"rs-6708933","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: CC-BY-4.0