{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:57:30Z","timestamp":1753869450072,"version":"3.41.2"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Molecular Recognition"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human interleukin\u20105 (IL\u20105) cytokine mediates the development of eosinophils and is involved in a variety of immune inflammatory responses that play a major role in the pathogenesis of childhood asthma, leukemia, and other pediatric allergic diseases. The immunomodulatory cytokine functions by binding to its cognate cell surface receptor IL\u20105R in a sheet\u2010by\u2010sheet manner, which can be conformationally mimicked and competitively disrupted by a double\u2010stranded cyclic AF18748 peptide. In this study, we systematically examined the co\u2010crystallized complex structure of human IL\u20105R with AF18748 peptide and rationally designed a halogen bond to glue at the protein\u2013peptide complex interface by substituting the indole moiety of AF18748 Trp13 residue with a halogen atom (X\u2009=\u2009F, Cl, Br, or I). High\u2010level theoretical calculations imparted presence of the halogen bond between the oxygen atom (\uf8feO) of IL\u20105R Glu58 backbone and the halogen atom (\uf8ffX) of AF18748 Trp13 side chain. Experimental assays confirmed that the halogen bond can promote peptide binding moderately or considerably. More importantly, the halogen bond not only enhances peptide affinity to IL\u20105R, but also improves peptide selectivity for its cognate IL\u20105R over other noncognate IL\u2010R proteins. As might be expected, the affinity and selectivity conferred by halogen bond increase consistently in the order: H\u2009&lt;\u2009F\u2009&lt;\u2009Cl\u2009&lt;\u2009Br\u2009&lt;\u2009I. Structural modeling revealed that the halogen bond plus its vicinal \u03c0\u2013cation\u2013\u03c0 stacking co\u2010define a ringed noncovalent system at the complex interface, which involves a synergistic effect to effectively improve the peptide binding potency and recognition specificity.<\/jats:p>","DOI":"10.1002\/jmr.3070","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T23:35:42Z","timestamp":1700782542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010based improvement of the binding affinity and recognition specificity of peptide competitors to target pediatric <scp>IL\u20105R<\/scp>\/<scp>IL<\/scp>\u20105 interaction by gluing halogen bonds at their complex interface"],"prefix":"10.1002","volume":"37","author":[{"given":"Peipei","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Pediatric Medicine Children's Hospital of Wujiang District, Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeping","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Children's Hospital of Wujiang District, Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chentao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Children's Hospital of Wujiang District, Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalin","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Children's Hospital of Wujiang District, Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjun","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Children's Hospital of Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiefan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Children's Hospital of Wujiang District, Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.07.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-5-1-30"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.119149"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.3.C623"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.07.044"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.02.042"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio237015a0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.158.3.822"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196902202800804"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1991.tb05725.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03854.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612023393800"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S78049"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14221"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0161"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110053997"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2003.10.012"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.12.489"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502341200"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202200175"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.11.029"},{"key":"e_1_2_8_23_1","first-page":"1","article-title":"Molecular design and systematic optimization of a halogen\u2010bonding system between the asthma interleukin receptor and its cyclic peptide ligand","volume":"102","author":"He Q","year":"2023","journal-title":"Chem Biol Drug Des"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.20001"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2020.213242"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202104089"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.23088"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8574"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/10610278.2020.1734203"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/pep2.24127"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b00429"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202201120"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10989-015-9501-9"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c01370"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.800857"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-022-03219-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200802019"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr5004419"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-011-9474-5"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.comptc.2012.04.010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2022.106916"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.2698"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac097"},{"key":"e_1_2_8_47_1","first-page":"1","article-title":"A structure\u2010based data set of protein\u2013peptide affinities and its nonredundant benchmark: potential applications in computational peptidology","volume":"30","author":"Wang S","year":"2023","journal-title":"Curr Med Chem"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-359141"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470559277.ch090102"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105382"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2201"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201500466"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/128_2014_551"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.3006"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.3014"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9MO00041K"}],"container-title":["Journal of Molecular Recognition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmr.3070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T09:48:58Z","timestamp":1707817738000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmr.3070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,21]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/jmr.3070"],"URL":"https:\/\/doi.org\/10.1002\/jmr.3070","archive":["Portico"],"relation":{},"ISSN":["0952-3499","1099-1352"],"issn-type":[{"type":"print","value":"0952-3499"},{"type":"electronic","value":"1099-1352"}],"subject":[],"published":{"date-parts":[[2023,11,21]]},"assertion":[{"value":"2023-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3070"}}