{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["de Araujo AD"],"funding":["National Health and Medical Research Council","Australian Research Council"],"pagination":["895-904"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9257625"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3(7)"],"pubmed_abstract":["Cyclic peptides that modulate protein-protein interactions can be valuable therapeutic candidates if they can be delivered intact to their target proteins in cells. Here we systematically compare the effects of different helix-inducing cyclization constraints on the capacity of a macrocyclic peptide component to confer α-helicity, protein-binding affinity, resistance to degradative proteases and cell uptake to a 12-residue peptide fragment of tumor suppressor protein p53. We varied the helix-inducing constraint (hydrocarbon, lactam, aliphatic or aromatic thioether, <i>etc.</i>) and the position of the cyclization linker (<i>i</i> to <i>i</i> + 4 or <i>i</i> to <i>i</i> + 7 bridges) in order to sculpt the macrocyclic size, stabilize its structure, and promote cell uptake. We find that rigid"],"journal":["RSC chemical biology"],"pubmed_title":["Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake."],"pmcid":["PMC9257625"],"funding_grant_id":["1128908","2009551","1145372","DP180103244","1117017","DP160104442","CE200100012"],"pubmed_authors":["de Araujo AD","Wu KC","Hoang HN","Lim J","Nguyen HT","Fairlie DP"],"additional_accession":[]},"is_claimable":false,"name":"Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake.","description":"Cyclic peptides that modulate protein-protein interactions can be valuable therapeutic candidates if they can be delivered intact to their target proteins in cells. Here we systematically compare the effects of different helix-inducing cyclization constraints on the capacity of a macrocyclic peptide component to confer α-helicity, protein-binding affinity, resistance to degradative proteases and cell uptake to a 12-residue peptide fragment of tumor suppressor protein p53. We varied the helix-inducing constraint (hydrocarbon, lactam, aliphatic or aromatic thioether, <i>etc.</i>) and the position of the cyclization linker (<i>i</i> to <i>i</i> + 4 or <i>i</i> to <i>i</i> + 7 bridges) in order to sculpt the macrocyclic size, stabilize its structure, and promote cell uptake. We find that rigid","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-04T12:40:50.682Z","creation":"2025-04-04T12:40:50.682Z"},"accession":"S-EPMC9257625","cross_references":{"pubmed":["35866171"],"doi":["10.1039/d1cb00231g"]}}