{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:01Z","timestamp":1787030101172,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T00:00:00Z","timestamp":1645228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["No. 2018YFB1304702"],"award-info":[{"award-number":["No. 2018YFB1304702"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 31970423"],"award-info":[{"award-number":["No. 31970423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.32071242"],"award-info":[{"award-number":["No.32071242"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The venomous species Deinagkistrodon acutus has been used as anti-inflammatory medicine in China for a long time. It has been proven to have anti-inflammatory activity, but its specific anti-inflammatory components have not yet been fully elucidated. Tumor necrosis factor receptor-1 (TNFR1), which participates in important intracellular signaling pathways, mediates apoptosis, and functions as a regulator of inflammation, is often used as the target to develop anti-inflammatory drugs. The small peptides of snake venom have the advantages of weak immunogenicity and strong activity. To obtain the specific TNFR1 binding peptides, we constructed a T7 phage library of D. acutus venom glands, and then performed biopanning against TNFR1 on the constructed library. After biopanning three times, several sequences with potential binding capacity were obtained and one 41-amino acid peptide was selected through a series of biological analyses including sequence length, solubility, and simulated affinity, named DAvp-1. After synthesis, the binding capacity of DAvp-1 and TNFR1 was verified using surface plasmon resonance technology (SPR). Conclusively, by applying phage display technology, this work depicts the successful screening of a promising peptide DAvp-1 from D. acutus venom that binds to TNFR1. Additionally, our study emphasizes the usefulness of phage display technology for studies on screening natural product components.<\/jats:p>","DOI":"10.3390\/toxins14020155","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:23:29Z","timestamp":1645431809000},"page":"155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Screening of TNFR1 Binding Peptides from Deinagkistrodon acutus Venom through Phage Display"],"prefix":"10.3390","volume":"14","author":[{"given":"Kangran","family":"Zhang","sequence":"first","affiliation":[{"name":"Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China"},{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-8721","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yezhong","family":"Tang","sequence":"additional","affiliation":[{"name":"Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev.bi.42.070173.001315","article-title":"Neurotoxins of animal venoms-snakes","volume":"42","author":"Tu","year":"1973","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.intimp.2015.01.017","article-title":"Antimicrobial peptide Cathelicidin-BF prevents intestinal barrier dysfunction in a mouse model of endotoxemia","volume":"25","author":"Song","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.intimp.2015.05.034","article-title":"Cathelicidin-BF suppresses intestinal inflammation by inhibiting the nuclear factor-kappa B signaling pathway and enhancing the phagocytosis of immune cells via STAT-1 in weanling piglets","volume":"28","author":"Yi","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16633","DOI":"10.1074\/jbc.M115.642645","article-title":"Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism","volume":"290","author":"Wei","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0092-8674(93)90132-A","article-title":"Crystal-structure of the soluble human 55 kd tnf receptor-human tnf-beta complex\u2014Implications for tnf receptor activation","volume":"73","author":"Banner","year":"1993","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1021\/acs.chemrev.7b00522","article-title":"Small Bioactive Peptides for Biomaterials Design and Therapeutics","volume":"117","author":"Hamley","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1016\/j.bmc.2017.09.011","article-title":"Therapeutic peptides for CNS indications: Progress and challenges","volume":"26","author":"Morimoto","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Apostolopoulos, V., Bojarska, J., Chai, T.T., Elnagdy, S., Kaczmarek, K., Matsoukas, J., New, R., Parang, K., Lopez, O.P., and Parhiz, H. (2021). A Global Review on Short Peptides: Frontiers and Perspectives. Molecules, 26.","DOI":"10.3390\/molecules26020430"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bios.2016.03.075","article-title":"Gold nanoprobe functionalized with specific fusion protein selection from phage display and its application in rapid, selective and sensitive colorimetric biosensing of Staphylococcus aureus","volume":"82","author":"Liu","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1021\/cr960065d","article-title":"Phage display","volume":"97","author":"Smith","year":"1997","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12954","DOI":"10.1073\/pnas.211439598","article-title":"T7 phage display: A novel genetic selection system for cloning RNA-binding proteins from cDNA libraries","volume":"98","author":"Danner","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","first-page":"883","article-title":"Identification of receptor ligands with phage display peptide libraries","volume":"40","author":"Koivunen","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"348409","DOI":"10.1155\/2013\/348409","article-title":"Phage Display Screening for Tumor Necrosis Factor-alpha-Binding Peptides: Detection of Inflammation in a Mouse Model of Hepatitis","volume":"2013","author":"Sclavons","year":"2013","journal-title":"Int. J. Pept."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5621","DOI":"10.4049\/jimmunol.161.10.5621","article-title":"A peptidomimetic antagonist of TNF-alpha-mediated cytotoxicity identified from a phage-displayed random peptide library","volume":"161","author":"Steward","year":"1998","journal-title":"J. Immunol."},{"key":"ref_15","first-page":"11","article-title":"Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis","volume":"6","author":"Zheng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, N.Y., Huang, Y., Li, A., Jiang, H.L., Wang, J., Li, J.Z., Qiu, L., Li, K., and Lu, Y.M. (2016). Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111940"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1600-065X.1999.tb01315.x","article-title":"On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease","volume":"169","author":"Kollias","year":"1999","journal-title":"Immunol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bbapap.2005.08.017","article-title":"MAPK signalling pathways as molecular targets for anti-inflammatory therapy\u2014From molecular mechanisms to therapeutic benefits","volume":"1754","author":"Kaminska","year":"2005","journal-title":"BBA-Proteins Proteom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41974","DOI":"10.18632\/oncotarget.9633","article-title":"The inflammatory\/cancer-related IL-6\/STAT3\/NF-kappa B positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts","volume":"7","author":"Hendrayani","year":"2016","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1152\/physrev.2001.81.2.807","article-title":"Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation","volume":"81","author":"Kyriakis","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.bbadis.2015.03.012","article-title":"Altered ROS production, NF-kappa B activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells","volume":"1852","author":"Altamirano","year":"2015","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.molmed.2017.11.002","article-title":"Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer","volume":"24","author":"Annibaldi","year":"2018","journal-title":"Trends Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/intimm\/dxz024","article-title":"TNF receptor signalling in autoinflammatory diseases","volume":"31","author":"Holbrook","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7457","DOI":"10.1021\/acs.chemrev.6b00716","article-title":"Super-Resolution Microscopy: Shedding Light on the Cellular Plasma Membrane","volume":"117","author":"Stone","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/ni.3790","article-title":"A guiding map for inflammation","volume":"18","author":"Netea","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/JLB.2AB0420-572RR","article-title":"Quantitative single-molecule imaging of TNFR1 reveals zafirlukast as antagonist of TNFR1 clustering and TNF alpha-induced NF-& x138;B signaling","volume":"109","author":"Weinelt","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.molimm.2009.01.007","article-title":"Tumor Necrosis Factor and the consequences of its ablation in vivo","volume":"47","author":"Efimov","year":"2009","journal-title":"Mol. Immunol."},{"key":"ref_28","first-page":"S152","article-title":"Side effects of anti-TNF therapy: Current knowledge","volume":"20","author":"Antoni","year":"2002","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/14728222.2019.1586886","article-title":"Tumor necrosis factor receptor-2 (TNFR2): An overview of an emerging drug target","volume":"23","author":"Medler","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41419-019-1456-x","article-title":"TNFRSF receptor-specific antibody fusion proteins with targeting controlled Fc gamma R-independent agonistic activity","volume":"10","author":"Medler","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1126\/scisignal.aav5637","article-title":"Noncompetitive inhibitors of TNFR1 probe conformational activation states","volume":"12","author":"Lo","year":"2019","journal-title":"Sci. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1177\/2472555217706478","article-title":"An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors","volume":"22","author":"Lo","year":"2017","journal-title":"Slas Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.drudis.2006.06.002","article-title":"Modulating TNF-alpha signaling with natural products","volume":"11","author":"Paul","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/0471143030.cb1704s17","article-title":"Mapping protein-protein interactions with phage-displayed combinatorial peptide libraries","volume":"17","author":"Kay","year":"2003","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2174\/0929867003375317","article-title":"Molecular modeling and computer aided drug design. Examples of their applications in medicinal chemistry","volume":"7","author":"Ooms","year":"2000","journal-title":"Curr. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/bs.apcsb.2017.06.003","article-title":"Structural prediction of protein-protein interactions by docking: Application to biomedical problems","volume":"Volume 110","author":"Donev","year":"2018","journal-title":"Protein-Protein Interactions in Human Disease, Pt A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1016\/j.bmcl.2016.04.049","article-title":"Solubility-driven lead optimisation: Recent examples and personal perspectives","volume":"26","author":"Ahmad","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/S0142-9612(00)00077-6","article-title":"Surface plasmon resonance analysis of dynamic biological interactions with biomaterials","volume":"21","author":"Green","year":"2000","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4155\/fmc-2016-0189","article-title":"Short peptides interfering with signaling pathways as new therapeutic tools for cancer treatment","volume":"9","author":"Poleszak","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_42","first-page":"95","article-title":"BioEdit: A user-friendly biological sequence alignment editorand analysis program for Windows 95\/98\/NT","volume":"41","author":"Hall","year":"1999","journal-title":"Nucl. Acids Symp. Ser."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/jmbi.1999.3091","article-title":"Protein secondary structure prediction based on position-specific scoring matrices","volume":"292","author":"Jones","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gky357","article-title":"HPEPDOCK: A web server for blind peptide-protein docking based on a hierarchical algorithm","volume":"46","author":"Zhou","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_45","unstructured":"Delano, W.L. (2021, October 20). The PyMOL Molecular Graphics System. Available online: http:\/\/www.pymol.org."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/2\/155\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:23:16Z","timestamp":1760134996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/2\/155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,19]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["toxins14020155"],"URL":"https:\/\/doi.org\/10.3390\/toxins14020155","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,19]]}}}