{"doi":"10.1515/bc.2009.072","title":"From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of <i>N-</i>glycans","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals (sugar coding). Here, we test the hypothesis that the common <jats:italic>N-</jats:italic>glycan modifications by core fucosylation and introduction of the bisecting <jats:italic>N</jats:italic>-acetylglucosamine moiety have long-range effects with functional consequences. Molecular dynamics simulations indicate a shift in conformational equilibria between linear extension or backfolding of the glycan antennae upon substitution. We also present a new fingerprint-like mode of presentation for this multi-parameter system. In order to delineate definite structure-function relationships, we strategically combined chemoenzymatic synthesis with bioassaying cell binding and the distribution of radioiodinated neoglycoproteins <jats:italic>in vivo</jats:italic>. Of clinical relevance, tailoring the core region affects serum clearance markedly, e.g., prolonging circulation time for the neoglycoprotein presenting the <jats:italic>N-</jats:italic>glycan with both substitutions. α2,3-Sialylation is another means toward this end, similarly seen for type II branching in triantennary <jats:italic>N</jats:italic>-glycans. This discovery signifies that rational glycoengineering along the given lines is an attractive perspective to optimize pharmacokinetic behavior of glycosylated pharmaproteins. Of general importance for the concept of the sugar code, the presented results teach the fundamental lesson that <jats:italic>N-</jats:italic>glycan core substitutions convey distinct characteristics to the concerned oligosaccharide relevant for <jats:italic>cis</jats:italic> and <jats:italic>trans</jats:italic> biorecognition processes. These modifications are thus molecular switches.</jats:p>","journal":"bchm","year":2009,"id":627038,"datarank":0.6732954554598211,"base_score":4.48863636973214,"endowment":4.48863636973214,"self_citation_contribution":0.6732954554598211,"citation_network_contribution":0.0,"self_endowment_contribution":0.6732954554598211,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":88,"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":1622421,"name":"Tibor Kožár","orcid":null,"position":1,"is_corresponding":false},{"id":1608550,"name":"Shuji Kojima","orcid":null,"position":2,"is_corresponding":false},{"id":409509,"name":"Carlo Unverzagt","orcid":"0000-0001-6492-1747","position":3,"is_corresponding":false},{"id":1608557,"name":"Hans-Joachim Gabius","orcid":null,"position":4,"is_corresponding":false},{"id":613816,"name":"Sabine André","orcid":"0000-0003-0850-0432","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of <i>N-</i>glycans","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals (sugar coding). Here, we test the hypothesis that the common <jats:italic>N-</jats:italic>glycan modifications by core fucosylation and introduction of the bisecting <jats:italic>N</jats:italic>-acetylglucosamine moiety have long-range effects with functional consequences. Molecular dynamics simulations indicate a shift in conformational equilibria between linear extension or backfolding of the glycan antennae upon substitution. We also present a new fingerprint-like mode of presentation for this multi-parameter system. In order to delineate definite structure-function relationships, we strategically combined chemoenzymatic synthesis with bioassaying cell binding and the distribution of radioiodinated neoglycoproteins <jats:italic>in vivo</jats:italic>. Of clinical relevance, tailoring the core region affects serum clearance markedly, e.g., prolonging circulation time for the neoglycoprotein presenting the <jats:italic>N-</jats:italic>glycan with both substitutions. α2,3-Sialylation is another means toward this end, similarly seen for type II branching in triantennary <jats:italic>N</jats:italic>-glycans. This discovery signifies that rational glycoengineering along the given lines is an attractive perspective to optimize pharmacokinetic behavior of glycosylated pharmaproteins. Of general importance for the concept of the sugar code, the presented results teach the fundamental lesson that <jats:italic>N-</jats:italic>glycan core substitutions convey distinct characteristics to the concerned oligosaccharide relevant for <jats:italic>cis</jats:italic> and <jats:italic>trans</jats:italic> biorecognition processes. These modifications are thus molecular switches.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19426132","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":null,"oa_locations":[{"url":"https://epub.ub.uni-muenchen.de/17744/1/bc.2009.072.pdf","host_type":"repository"},{"url":"http://www.degruyter.com/view/j/bchm.2009.390.issue-7/bc.2009.072/bc.2009.072.xml","host_type":"publisher"},{"url":"https://www.degruyter.com/document/doi/10.1515/BC.2009.072/xml","host_type":"publisher"},{"url":"https://www.degruyter.com/document/doi/10.1515/BC.2009.072/pdf","host_type":"publisher"}],"fields_of_study":["Animals","Carbohydrate Conformation","Cells","Glycomics","Humans","Lectins","Polysaccharides","Protein Binding"],"mesh_terms":["Animals","Carbohydrate Conformation","Cells","Glycomics","Humans","Lectins","Polysaccharides","Protein Binding"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T16:02:38.941376Z","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":[]}