{"doi":"10.1002/chem.202200146","title":"Synthetic Antibody‐Rhamnose Cluster Conjugates Show Potent Complement‐Dependent Cell Killing by Recruiting Natural Antibodies","abstract":"Monoclonal antibodies (mAbs) are one of the most rapidly growing drug classes used for the treatment of cancer, infectious and autoimmune diseases. Complement-dependent cytotoxicity (CDC) is one of the effector functions for antibodies to deplete target cells. We report here an efficient chemoenzymatic synthesis of structurally well-defined conjugates of a monoclonal antibody with a rhamnose- and an αGal trisaccharide-cluster to recruit natural anti-rhamnose and anti-αGal antibodies, respectively, to enhance the CDC-dependent targeted cell killing. The synthesis was achieved by using a modular antibody Fc-glycan remodeling method that includes site-specific chemoenzymatic Fc-glycan functionalization and subsequent click conjugation of synthetic rhamnose- and αGal trisaccharide-cluster to provide the respective homogeneous antibody conjugates. Cell-based assays indicated that the antibody-rhamnose cluster conjugates could mediate potent CDC activity for targeted cancer cell killing and showed much more potent efficacy than the antibody-αGal trisaccharide cluster conjugates for CDC effects.","journal":"Chemistry - A European Journal","year":2022,"id":254072,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"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":648682,"name":"Sunaina Kiran Prabhu","orcid":"0000-0003-0847-3059","position":1,"is_corresponding":false},{"id":761057,"name":"Xiao Zhang","orcid":"0000-0001-5569-671X","position":2,"is_corresponding":false},{"id":355882,"name":"Guanghui Zong","orcid":"0000-0002-7335-039X","position":3,"is_corresponding":false},{"id":476827,"name":"Qiang Yang","orcid":"0000-0001-8367-1755","position":4,"is_corresponding":false},{"id":355883,"name":"Lai‐Xi Wang","orcid":"0000-0003-4293-5819","position":5,"is_corresponding":false},{"id":672860,"name":"Chong Ou","orcid":"0000-0001-7926-1059","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T00:25:03.918844Z","pmid":"35106843","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":[]}