{"doi":"10.1002/psc.2872","title":"An efficient solid‐phase synthesis of peptidyl‐<i>N</i>‐acetylguanidines for use in native chemical ligation","abstract":"<jats:p>In the modern protocols of chemical protein syntheses, peptide‐α‐thioesters have been used as key components for the assembly of full‐length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide‐α‐thioesters by Fmoc solid phase peptide synthesis (Fmoc‐SPPS). Recently our group found a peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidine as a new peptide‐α‐thioester precursor. This peptide derivative can be converted into a corresponding peptide‐α‐thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid‐phase synthesis of peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidines from the on‐resin protected peptides prepared by standard Fmoc‐SPPS. We also evaluated the reactivity of a peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidine in native chemical ligation through the synthesis of glucose‐dependent insulinotropic polypeptide analogue. Copyright © 2016 European Peptide Society and John Wiley &amp; Sons, Ltd.</jats:p>","journal":"Journal of Peptide Science","year":2016,"id":682792,"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":1783703,"name":"Madoka Isoe","orcid":null,"position":1,"is_corresponding":false},{"id":70889,"name":"Masayuki Izumi","orcid":"0000-0001-6486-9678","position":2,"is_corresponding":false},{"id":70895,"name":"Yasuhiro Kajihara","orcid":"0000-0002-6656-2394","position":3,"is_corresponding":false},{"id":70891,"name":"Ryo Okamoto","orcid":"0000-0001-9529-2525","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An efficient solid‐phase synthesis of peptidyl‐<i>N</i>‐acetylguanidines for use in native chemical ligation","abstract":"<jats:p>In the modern protocols of chemical protein syntheses, peptide‐α‐thioesters have been used as key components for the assembly of full‐length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide‐α‐thioesters by Fmoc solid phase peptide synthesis (Fmoc‐SPPS). Recently our group found a peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidine as a new peptide‐α‐thioester precursor. This peptide derivative can be converted into a corresponding peptide‐α‐thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid‐phase synthesis of peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidines from the on‐resin protected peptides prepared by standard Fmoc‐SPPS. We also evaluated the reactivity of a peptidyl‐<jats:italic>N</jats:italic>‐acetylguanidine in native chemical ligation through the synthesis of glucose‐dependent insulinotropic polypeptide analogue. Copyright © 2016 European Peptide Society and John Wiley &amp; Sons, Ltd.</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":"27005965","pmcid":null,"openalex_id":"https://openalex.org/W2305680759","authors":[],"funders":[{"funder_name":"JSPS KAKENHI","grant_id":"24750161","title":null}],"total_grants":1,"fwci":0.8543,"citation_percentile":0.75424118,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":3},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2025,"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%2Fpsc.2872","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/psc.2872","host_type":"publisher"},{"url":"https://doi.org/10.1002/psc.2872","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27005965","host_type":"repository"}],"fields_of_study":["Chemical Synthesis and Analysis","Peptidase Inhibition and Analysis","Antimicrobial Peptides and Activities","Esters","Hydrogen-Ion Concentration","Molecular Structure","Peptides","Solid-Phase Synthesis Techniques"],"mesh_terms":["Esters","Hydrogen-Ion Concentration","Peptides","Molecular Structure","Solid-Phase Synthesis Techniques"],"keywords":["Thioester","Native chemical ligation","Peptide","Chemistry","Chemical ligation","Peptide synthesis","Combinatorial chemistry","Solid-phase synthesis","Chemical synthesis","Stereochemistry","Cleavage (geology)","Peptide bond","Organic chemistry","Biochemistry","In vitro","Enzyme","Chemical Protein Synthesis","Peptide-α-thioester","Peptidyl-n-acetylguanidine","Thioester Precursor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T21:22:51.588622Z","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":[]}