{"doi":"10.1016/j.apsb.2022.10.014","title":"α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo","abstract":"Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t1/2 > 14 days) compared to t1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.","journal":"Acta Pharmaceutica Sinica B","year":2022,"id":267782,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":752690,"name":"Candy Lee","orcid":null,"position":1,"is_corresponding":false},{"id":300808,"name":"Peng Sang","orcid":"0000-0002-8336-4533","position":2,"is_corresponding":false},{"id":928908,"name":"Zaid Amso","orcid":"0000-0002-8724-2445","position":3,"is_corresponding":false},{"id":418220,"name":"David Huang","orcid":"0000-0003-2592-8393","position":4,"is_corresponding":false},{"id":622496,"name":"Weixia Zhong","orcid":null,"position":5,"is_corresponding":false},{"id":422935,"name":"Meng Gu","orcid":null,"position":6,"is_corresponding":false},{"id":751941,"name":"Lulu Wei","orcid":"0000-0003-4657-9479","position":7,"is_corresponding":false},{"id":928909,"name":"Vân Nguyên-Trân","orcid":"0000-0001-5678-1908","position":8,"is_corresponding":false},{"id":928910,"name":"Jingyao Zhang","orcid":"0000-0002-8227-9396","position":9,"is_corresponding":false},{"id":469946,"name":"Weijun Shen","orcid":"0000-0001-8388-729X","position":10,"is_corresponding":false},{"id":300813,"name":"Jianfeng Cai","orcid":"0000-0003-3106-3306","position":11,"is_corresponding":false},{"id":300809,"name":"Yan Shi","orcid":"0000-0002-4086-6103","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T00:27:06.198948Z","pmid":"37139407","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":[]}