{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Otero-Ramirez ME"],"funding":["Japan Agency for Medical Research and Development","Ministry of Education, Culture, Sports, Science and Technology"],"pagination":["26-34"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8382136"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["1(1)"],"pubmed_abstract":["Here we report <i>de novo</i> macrocyclic peptide binders to Wnt3a, a member of the Wnt protein family. By means of the Random non-standard Peptides Integrated Discovery (RaPID) system, we have performed <i>in vitro</i> selection against the complex of mouse Wnt3a (mWnt3a) with human afamin (hAFM) to discover macrocyclic peptides that bind mWnt3a with <i>K</i> <sub>D</sub> values as tight as 110 nM. One of these peptides, WAp-D04 (Wnt-AFM-peptide-D04), was able to inhibit the receptor-mediated signaling process, which was demonstrated in a Wnt3a-dependent reporter cell-line. Based on this initial hit, we applied a block-mutagenesis scanning display to identify a mutant inhibitor, WAp-D04-W10P, with 5-fold greater potency in a reporter assay. This work represents the first instance of molecules capable of inhibiting Wnt signaling through direct interaction with a Wnt protein, a molecular class for which targeting has been challenging due its highly hydrophobic nature."],"journal":["RSC chemical biology"],"pubmed_title":["Macrocyclic peptides that inhibit Wnt signalling <i>via</i> interaction with Wnt3a."],"pmcid":["PMC8382136"],"funding_grant_id":["JP17H01420","JP19am0101075","JP19am0101090"],"pubmed_authors":["Takagi J","Mihara E","Suga H","Otero-Ramirez ME","Matoba K","Passioura T"],"additional_accession":[]},"is_claimable":false,"name":"Macrocyclic peptides that inhibit Wnt signalling <i>via</i> interaction with Wnt3a.","description":"Here we report <i>de novo</i> macrocyclic peptide binders to Wnt3a, a member of the Wnt protein family. By means of the Random non-standard Peptides Integrated Discovery (RaPID) system, we have performed <i>in vitro</i> selection against the complex of mouse Wnt3a (mWnt3a) with human afamin (hAFM) to discover macrocyclic peptides that bind mWnt3a with <i>K</i> <sub>D</sub> values as tight as 110 nM. One of these peptides, WAp-D04 (Wnt-AFM-peptide-D04), was able to inhibit the receptor-mediated signaling process, which was demonstrated in a Wnt3a-dependent reporter cell-line. Based on this initial hit, we applied a block-mutagenesis scanning display to identify a mutant inhibitor, WAp-D04-W10P, with 5-fold greater potency in a reporter assay. This work represents the first instance of molecules capable of inhibiting Wnt signaling through direct interaction with a Wnt protein, a molecular class for which targeting has been challenging due its highly hydrophobic nature.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Apr","modification":"2024-11-21T11:00:28.079Z","creation":"2022-02-11T09:58:47.626Z"},"accession":"S-EPMC8382136","cross_references":{"pubmed":["34458746"],"doi":["10.1039/d0cb00016g"]}}