{"doi":"10.1002/cbic.201700075","title":"A New Methodology for Incorporating Chiral Linkers into Stapled Peptides","abstract":"<jats:title>Abstract</jats:title><jats:p>Stapled peptides have arisen as a new class of chemical probe and potential therapeutic agents for modulating protein–protein interactions. Here, we report the first two‐component <jats:italic>i</jats:italic>,<jats:italic>i</jats:italic>+7 stapling methodology that makes use of two orthogonal, on‐resin stapling reactions to incorporate linkers bearing a chiral centre into a p53‐derived stapled peptide. Post‐stapling modifications to the chain were performed on‐resin and enabled rapid access to various peptide derivatives from a single staple. The stapled peptides have increased helicity, protease stability and in vitro binding affinities to MDM2 compared to the equivalent unstapled peptide. This approach can be used to generate a library of diverse stapled peptides with different properties starting from a single stapled peptide, with scope for much greater functional diversity than that provided by existing stapling methodologies.</jats:p>","journal":"ChemBioChem","year":2017,"id":43850,"datarank":1.1323917523020242,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.6556836777498322,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.6556836777498322,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":21,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":1,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":207505,"name":"James Sipthorp","orcid":"0000-0002-6838-8043","position":1,"is_corresponding":false},{"id":207506,"name":"Wenshu Xu","orcid":null,"position":2,"is_corresponding":false},{"id":207507,"name":"Laura S. Itzhaki","orcid":"0000-0001-6504-2576","position":3,"is_corresponding":false},{"id":207508,"name":"Steven V. Ley","orcid":"0000-0002-7816-0042","position":4,"is_corresponding":false},{"id":207504,"name":"Juan C. 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