{"id":"https://openalex.org/W7223344233","doi":"https://doi.org/10.26434/chemrxiv.15010946/v1","title":"A Direct-to-Biology Platform for Rapid Covalent Antibiotic Discovery","display_name":"A Direct-to-Biology Platform for Rapid Covalent Antibiotic Discovery","publication_year":2026,"publication_date":"2026-10-23","ids":{"openalex":"https://openalex.org/W7223344233","doi":"https://doi.org/10.26434/chemrxiv.15010946/v1"},"language":"en","primary_location":{"id":"doi:10.26434/chemrxiv.15010946/v1","doi":"https://doi.org/10.26434/chemrxiv.15010946/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010946/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010946/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010946/v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5047012339","display_name":"Storm van der Voort","orcid":"https://orcid.org/0000-0001-8177-1496","observed_orcids":["https://orcid.org/0000-0001-8177-1496"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Storm van der Voort","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":"https://orcid.org/0000-0001-8177-1496","affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075007882","display_name":"Tessa A. Got\u00e9","orcid":"https://orcid.org/0000-0003-3588-7732","observed_orcids":["https://orcid.org/0000-0003-3588-7732"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Tessa Got\u00e9","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159311259","display_name":"Sophie van \u2018t Ooster","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Sophie van \u2018t Ooster","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029304706","display_name":"Berend Gagestein","orcid":"https://orcid.org/0000-0002-0993-6812","observed_orcids":["https://orcid.org/0000-0002-0993-6812"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Berend Gagestein","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000584872","display_name":"Bogdan I. Florea","orcid":"https://orcid.org/0000-0001-7114-2266","observed_orcids":["https://orcid.org/0000-0001-7114-2266"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Bogdan I. Florea","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010939408","display_name":"Richard J. B. H. N. van den Berg","orcid":"https://orcid.org/0000-0002-8585-3904","observed_orcids":["https://orcid.org/0000-0002-8585-3904"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Richard J. B. H. N. van den Berg","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003260841","display_name":"Zachary Armstrong","orcid":"https://orcid.org/0000-0002-4086-2946","observed_orcids":["https://orcid.org/0000-0002-4086-2946"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Zachary Armstrong","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056673744","display_name":"Herman S. Overkleeft","orcid":"https://orcid.org/0000-0001-6976-7005","observed_orcids":["https://orcid.org/0000-0001-6976-7005"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Herman S. Overkleeft","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5022205362","display_name":"Stephan M. Hacker","orcid":"https://orcid.org/0000-0001-5420-4824","observed_orcids":["https://orcid.org/0000-0001-5420-4824"]},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Stephan M. Hacker","raw_affiliation_strings":["Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC"],"raw_orcid":"https://orcid.org/0000-0001-5420-4824","affiliations":[{"raw_affiliation_string":"Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden, Netherlands, 2333 CC","institution_ids":["https://openalex.org/I121797337"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I121797337"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11440","display_name":"Click Chemistry and Applications","score":0.8871999979019165,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11440","display_name":"Click Chemistry and Applications","score":0.8871999979019165,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.06520000100135803,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10252","display_name":"Microbial Natural Products and Biosynthesis","score":0.006800000090152025,"subfield":{"id":"https://openalex.org/subfields/2402","display_name":"Applied Microbiology and Biotechnology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/antibiotic-discovery","display_name":"antibiotic discovery","score":0.7459999918937683},{"id":"https://openalex.org/keywords/chloroacetamide","display_name":"chloroacetamide","score":0.8199999928474426},{"id":"https://openalex.org/keywords/copper-catalyzed-azide-alkyne-cycloaddition","display_name":"copper-catalyzed azide-alkyne cycloaddition","score":0.9919999837875366},{"id":"https://openalex.org/keywords/combinatorial-synthesis","display_name":"combinatorial synthesis","score":0.7799999713897705},{"id":"https://openalex.org/keywords/methicillin-resistant-staphylococcus-aureus","display_name":"methicillin-resistant Staphylococcus aureus","score":0.9309999942779541},{"id":"https://openalex.org/keywords/hmg-coa-synthase","display_name":"HMG-CoA synthase","score":0.9129999876022339},{"id":"https://openalex.org/keywords/chemoproteomics","display_name":"chemoproteomics","score":0.9620000123977661},{"id":"https://openalex.org/keywords/co-crystal-structure","display_name":"co-crystal structure","score":0.9139999747276306},{"id":"https://openalex.org/keywords/antibiotic-resistance","display_name":"antibiotic resistance","score":0.6140000224113464}],"concepts":[{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.7524999976158142},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.599399983882904},{"id":"https://openalex.org/C501593827","wikidata":"https://www.wikidata.org/wiki/Q12187","display_name":"Antibiotics","level":2,"score":0.5616999864578247},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.5223000049591064},{"id":"https://openalex.org/C2776904781","wikidata":"https://www.wikidata.org/wiki/Q424424","display_name":"Diazo","level":2,"score":0.48429998755455017},{"id":"https://openalex.org/C2777814067","wikidata":"https://www.wikidata.org/wiki/Q1752317","display_name":"Tandem","level":2,"score":0.45410001277923584},{"id":"https://openalex.org/C2779489039","wikidata":"https://www.wikidata.org/wiki/Q188121","display_name":"Staphylococcus aureus","level":3,"score":0.4237000048160553},{"id":"https://openalex.org/C2780183148","wikidata":"https://www.wikidata.org/wiki/Q21099571","display_name":"Lipid II","level":4,"score":0.4108999967575073},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.38850000500679016},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3840000033378601},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.34470000863075256},{"id":"https://openalex.org/C547475151","wikidata":"https://www.wikidata.org/wiki/Q25419","display_name":"Escherichia coli","level":3,"score":0.3212999999523163},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.3165000081062317},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3124000132083893},{"id":"https://openalex.org/C523546767","wikidata":"https://www.wikidata.org/wiki/Q10876","display_name":"Bacteria","level":2,"score":0.27300000190734863},{"id":"https://openalex.org/C35753019","wikidata":"https://www.wikidata.org/wiki/Q644785","display_name":"Total synthesis","level":2,"score":0.2727000117301941},{"id":"https://openalex.org/C57992300","wikidata":"https://www.wikidata.org/wiki/Q2066956","display_name":"Potency","level":3,"score":0.27219998836517334},{"id":"https://openalex.org/C3018522384","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent binding","level":3,"score":0.26429998874664307},{"id":"https://openalex.org/C4937899","wikidata":"https://www.wikidata.org/wiki/Q68541106","display_name":"Antimicrobial","level":2,"score":0.2630000114440918},{"id":"https://openalex.org/C171250308","wikidata":"https://www.wikidata.org/wiki/Q11468","display_name":"Nanotechnology","level":1,"score":0.257099986076355},{"id":"https://openalex.org/C15151743","wikidata":"https://www.wikidata.org/wiki/Q903778","display_name":"Metagenomics","level":3,"score":0.2558000087738037}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.26434/chemrxiv.15010946/v1","doi":"https://doi.org/10.26434/chemrxiv.15010946/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010946/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010946/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.26434/chemrxiv.15010946/v1","doi":"https://doi.org/10.26434/chemrxiv.15010946/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010946/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010946/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.4043000042438507,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2882641128","display_name":"SULFOPROBE: Towards new chemical tools to investigate mucin degradation at the host-microbiome interface","funder_award_id":"OCENW.M.24.135","funder_id":"https://openalex.org/F4320321800","funder_display_name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek"}],"funders":[{"id":"https://openalex.org/F4320321800","display_name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","ror":"https://ror.org/04jsz6e67"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7223344233.pdf","grobid_xml":"https://content.openalex.org/works/W7223344233.grobid-xml"},"referenced_works_count":33,"referenced_works":["https://openalex.org/W2014918546","https://openalex.org/W2018339027","https://openalex.org/W2049504060","https://openalex.org/W2059534238","https://openalex.org/W2144240948","https://openalex.org/W2152640773","https://openalex.org/W2328302082","https://openalex.org/W2409710550","https://openalex.org/W2430132928","https://openalex.org/W2978551904","https://openalex.org/W2979805180","https://openalex.org/W2984504859","https://openalex.org/W2990159340","https://openalex.org/W3016772376","https://openalex.org/W3112376646","https://openalex.org/W3140499454","https://openalex.org/W3147806186","https://openalex.org/W3189939557","https://openalex.org/W4206677002","https://openalex.org/W4313339505","https://openalex.org/W4365146810","https://openalex.org/W4389670170","https://openalex.org/W4399809846","https://openalex.org/W4400879144","https://openalex.org/W4402557213","https://openalex.org/W4408022373","https://openalex.org/W4408193052","https://openalex.org/W4409430637","https://openalex.org/W4413960510","https://openalex.org/W4415692556","https://openalex.org/W7116909429","https://openalex.org/W7130642772","https://openalex.org/W7166714539"],"related_works":["https://openalex.org/W7140925137","https://openalex.org/W4391135580","https://openalex.org/W3036235537","https://openalex.org/W4295419429","https://openalex.org/W2318337237","https://openalex.org/W2894420701","https://openalex.org/W3171419022","https://openalex.org/W4391375816","https://openalex.org/W4385805586","https://openalex.org/W1965626949"],"abstract_inverted_index":{"The":[0],"rise":[1],"of":[2,28,61,91,102,128,137],"antibiotic-resistant":[3],"bacterial":[4],"infections":[5],"has":[6],"created":[7],"a":[8,37,59,119,150],"critical":[9],"need":[10],"for":[11,40,66],"new":[12],"antibiotics.":[13],"While":[14],"natural":[15],"product-based":[16],"covalent":[17,30,41],"antibiotic":[18,42],"classes":[19],"such":[20],"as":[21],"the":[22,92,103,109,125,129],"\u03b2-lactams":[23],"are":[24],"highly":[25],"effective,":[26],"exploration":[27],"synthetic":[29],"antibiotics":[31],"remains":[32],"limited.":[33],"Here,":[34],"we":[35,52],"present":[36],"direct-to-biology":[38],"platform":[39,133],"discovery.":[43],"Using":[44],"tandem":[45],"diazo":[46],"transfer":[47],"and":[48,63,75,117,144],"copper-catalyzed":[49],"azide-alkyne":[50],"cycloaddition,":[51],"combinatorially":[53],"synthesized":[54],"720":[55],"crude":[56],"chloroacetamides":[57],"within":[58,149],"matter":[60],"days":[62],"screened":[64],"these":[65],"activity":[67],"against":[68],"methicillin-resistant":[69],"Staphylococcus":[70],"aureus":[71],"(MRSA).":[72],"By":[73],"resynthesis":[74],"retesting,":[76],"almost":[77],"all":[78],"hits":[79],"were":[80],"confirmed":[81],"to":[82,89,122],"be":[83],"active,":[84],"having":[85],"potency":[86],"profiles":[87],"comparable":[88],"those":[90],"initial":[93],"screen.":[94],"In":[95],"situ":[96],"chemoproteomic":[97],"analyses":[98],"revealed":[99],"selective":[100],"engagement":[101],"essential":[104],"enzyme":[105],"HMG-CoA":[106],"synthase":[107],"by":[108],"most":[110],"promising":[111],"hits.":[112],"We":[113],"validated":[114],"this":[115,132],"target":[116],"obtained":[118],"co-crystal":[120],"structure":[121],"better":[123],"understand":[124],"binding":[126],"mode":[127],"compound.":[130],"Altogether,":[131],"generates":[134],"large":[135],"libraries":[136],"covalently":[138],"reactive":[139],"compounds,":[140,143],"identifies":[141],"active":[142],"finds":[145],"their":[146],"molecular":[147],"targets":[148],"single":[151],"screening":[152],"campaign.":[153]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-24T00:00:00"}