{"doi":"10.1002/anie.201408126","title":"A Noncanonical Function of Sortase Enables Site‐Specific Conjugation of Small Molecules to Lysine Residues in Proteins","abstract":"<jats:title>Abstract</jats:title><jats:p>We provide the first demonstration that isopeptide ligation, a noncanonical activity of the enzyme sortase A, can be used to modify recombinant proteins. This reaction was used in vitro to conjugate small molecules to a peptide, an engineered targeting protein, and a full‐length monoclonal antibody with an exquisite level of control over the site of conjugation. Attachment to the protein substrate occurred exclusively through isopeptide bonds at a lysine ε‐amino group within a specific amino acid sequence. This reaction allows more than one molecule to be site‐specifically conjugated to a protein at internal sites, thereby overcoming significant limitations of the canonical native peptide ligation reaction catalyzed by sortase A. Our method provides a unique chemical ligation procedure that is orthogonal to existing methods, supplying a new method to site‐specifically modify lysine residues that will be a valuable addition to the protein conjugation toolbox.</jats:p>","journal":"Angewandte Chemie International Edition","year":2015,"id":682246,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"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":724309,"name":"Jayanta Bhattacharyya","orcid":"0000-0003-0202-4770","position":1,"is_corresponding":false},{"id":231603,"name":"Ashutosh Chilkoti","orcid":"0000-0002-1569-2228","position":2,"is_corresponding":false},{"id":1782383,"name":"Joseph J. 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This reaction allows more than one molecule to be site‐specifically conjugated to a protein at internal sites, thereby overcoming significant limitations of the canonical native peptide ligation reaction catalyzed by sortase A. Our method provides a unique chemical ligation procedure that is orthogonal to existing methods, supplying a new method to site‐specifically modify lysine residues that will be a valuable addition to the protein conjugation toolbox.</jats:p>","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25363491","pmcid":"PMC4314310","openalex_id":"https://openalex.org/W2124825194","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM061232","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"5T32 GM008487","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008487","title":null}],"total_grants":3,"fwci":3.2501,"citation_percentile":0.92997329,"influential_citations":0,"citation_trend":[{"year":2015,"count":6},{"year":2016,"count":8},{"year":2017,"count":11},{"year":2018,"count":6},{"year":2019,"count":3},{"year":2020,"count":5},{"year":2021,"count":5},{"year":2022,"count":3},{"year":2023,"count":3},{"year":2024,"count":5},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fanie.201408126","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201408126","host_type":"publisher"},{"url":"https://doi.org/10.1002/anie.201408126","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25363491","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4314310","host_type":"repository"}],"fields_of_study":["Biochemical and Structural Characterization","Glycosylation and Glycoproteins Research","Peptidase Inhibition and Analysis"],"mesh_terms":["Bacterial Proteins","Lysine","Proteins"],"keywords":["Sortase","Sortase A","Lysine","Conjugate","Peptide","Chemistry","Peptide bond","Chemical ligation","Ligation","Conjugated system","Amino acid","Combinatorial chemistry","Small molecule","Biochemistry","Substrate (aquarium)","Peptide sequence","Stereochemistry","Biology","Molecular biology","Polymer","Organic chemistry","Biotechnology","Bioconjugation","Protein Modification"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T19:51:35.445868Z","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":[]}