{"doi":"10.1002/cbic.202100502","title":"Binding Methylarginines and Methyllysines as Free Amino Acids: A Comparative Study of Multiple Host Classes**","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Methylated free amino acids are an important class of targets for host‐guest chemistry that have recognition properties distinct from those of methylated peptides and proteins. We present comparative binding studies for three different host classes that are each studied with multiple methylated arginines and lysines to determine fundamental structure‐function relationships. The hosts studied are all anionic and include three calixarenes, two acyclic cucurbiturils, and two other cleft‐like hosts, a clip and a tweezer. We determined the binding association constants for a panel of methylated amino acids using indicator displacement assays. The acyclic cucurbiturils display stronger binding to the methylated amino acids, and some unique patterns of selectivity. The two other cleft‐like hosts follow two different trends, shallow host (clip) following similar trends to the calixarenes, and the other more closed host (tweezer) binding certain less‐methylated amino acids stronger than their methylated counterparts. Molecular modelling sheds some light on the different preferences of the various hosts. The results identify hosts with new selectivities and with affinities in a range that could be useful for biomedical applications. The overall selectivity patterns are explained by a common framework that considers the geometry, depth of binding pockets, and functional group participation across all host classes.</jats:p>","journal":"ChemBioChem","year":2022,"id":612415,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"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":1576816,"name":"Bianca E. Kamba","orcid":"0000-0001-9594-1492","position":1,"is_corresponding":false},{"id":1576817,"name":"My‐Hue Le","orcid":"0000-0002-7397-4709","position":2,"is_corresponding":false},{"id":297527,"name":"Thomas Schräder","orcid":"0000-0002-7003-6362","position":3,"is_corresponding":false},{"id":301914,"name":"Lyle Isaacs","orcid":"0000-0002-4079-332X","position":4,"is_corresponding":false},{"id":1576818,"name":"Peter Bayer","orcid":"0000-0003-0435-7202","position":5,"is_corresponding":false},{"id":602272,"name":"Fraser Hof","orcid":"0000-0003-4658-9132","position":6,"is_corresponding":false},{"id":1576815,"name":"Zoey Warmerdam","orcid":"0000-0002-9640-6712","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Binding Methylarginines and Methyllysines as Free Amino Acids: A Comparative Study of Multiple Host Classes**","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Methylated free amino acids are an important class of targets for host‐guest chemistry that have recognition properties distinct from those of methylated peptides and proteins. We present comparative binding studies for three different host classes that are each studied with multiple methylated arginines and lysines to determine fundamental structure‐function relationships. The hosts studied are all anionic and include three calixarenes, two acyclic cucurbiturils, and two other cleft‐like hosts, a clip and a tweezer. We determined the binding association constants for a panel of methylated amino acids using indicator displacement assays. The acyclic cucurbiturils display stronger binding to the methylated amino acids, and some unique patterns of selectivity. The two other cleft‐like hosts follow two different trends, shallow host (clip) following similar trends to the calixarenes, and the other more closed host (tweezer) binding certain less‐methylated amino acids stronger than their methylated counterparts. Molecular modelling sheds some light on the different preferences of the various hosts. The results identify hosts with new selectivities and with affinities in a range that could be useful for biomedical applications. The overall selectivity patterns are explained by a common framework that considers the geometry, depth of binding pockets, and functional group participation across all host classes.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34758178","pmcid":"PMC9299052","openalex_id":"https://openalex.org/W3213182364","authors":[],"funders":[{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"RGPIN-2019-04806","title":null},{"funder_name":"National Science Foundation","grant_id":"CHE-1807486","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft (DFG)","grant_id":"BA1624/15-1","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft (DFG)","grant_id":"Schr 604/19-1","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Science Foundation","grant_id":"1807486","title":"Synthesis and Recognition Properties of Cucurbit[n]uril Type Receptors"}],"total_grants":6,"fwci":0.4441,"citation_percentile":0.59188061,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbic.202100502","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbic.202100502","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/cbic.202100502","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cbic.202100502","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/cbic.202100502","host_type":"publisher"},{"url":"https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/cbic.202100502","host_type":"publisher"},{"url":"https://doi.org/10.1002/cbic.202100502","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34758178","host_type":"repository"},{"url":"http://hdl.handle.net/1828/13825","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9299052","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9299052","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9299052?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1002/cbic.202100502","host_type":""},{"url":"https://dx.doi.org/10.1002/cbic.202100502","host_type":""},{"url":"https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85119691218","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pubmed/34758178","host_type":""}],"fields_of_study":["Chemical Synthesis and Analysis","Supramolecular Chemistry and Complexes","Fluorine in Organic Chemistry","01 natural sciences","0104 chemical sciences","Amino Acids","Arginine","Lysine","Methylation","Protein Binding"],"mesh_terms":["Amino Acids","Arginine","Lysine","Methylation","Protein Binding"],"keywords":["Cucurbituril","Binding affinities","Amino acid","Affinities","Chemistry","Binding selectivity","Host (biology)","Stereochemistry","Selectivity","Methylation","Biochemistry","Biology","Organic chemistry","Supramolecular chemistry","Molecule","DNA","Genetics","Macrocycles","Host-guest Chemistry","Methylated Amino Acids","Indicator Displacement Assays","Lysine","Chemie","Full Papers","Amino Acids","Arginine","Protein Binding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T03:18:32.871495Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}