{"id":"https://openalex.org/W7213400029","doi":"https://doi.org/10.26434/chemrxiv.15008909/v1","title":"Synthetic Mutagenesis of Tyrosine into Proline Mimetics Enables Late-Stage Backbone Editing of Peptides","display_name":"Synthetic Mutagenesis of Tyrosine into Proline Mimetics Enables Late-Stage Backbone Editing of Peptides","publication_year":2026,"publication_date":"2026-09-16","ids":{"openalex":"https://openalex.org/W7213400029","doi":"https://doi.org/10.26434/chemrxiv.15008909/v1"},"language":"en","primary_location":{"id":"doi:10.26434/chemrxiv.15008909/v1","doi":"https://doi.org/10.26434/chemrxiv.15008909/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15008909/v1","pdf_url":null,"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":"submittedVersion","is_accepted":false,"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://doi.org/10.26434/chemrxiv.15008909/v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5051522294","display_name":"Takaya Togo","orcid":"https://orcid.org/0000-0003-0243-0760","observed_orcids":["https://orcid.org/0000-0003-0243-0760"]},"institutions":[{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takaya Togo","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","institution_ids":["https://openalex.org/I74801974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080373988","display_name":"Takumi Ueda","orcid":"https://orcid.org/0000-0001-9677-0912","observed_orcids":["https://orcid.org/0000-0001-9677-0912"]},"institutions":[{"id":"https://openalex.org/I98285908","display_name":"The University of Osaka","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takumi Ueda","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka, Japan, 565-0871"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka, Japan, 565-0871","institution_ids":["https://openalex.org/I98285908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022044182","display_name":"Yuko Otani","orcid":"https://orcid.org/0000-0002-8104-283X","observed_orcids":["https://orcid.org/0000-0002-8104-283X"]},"institutions":[{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yuko Otani","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","institution_ids":["https://openalex.org/I74801974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5126208499","display_name":"Yuka Furukawa","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I73613424","display_name":"National Institute of Advanced Industrial Science and Technology","ror":"https://ror.org/01703db54","country_code":"JP","type":"government","lineage":["https://openalex.org/I73613424"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yuka Furukawa","raw_affiliation_strings":["Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan, 305-8577"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan, 305-8577","institution_ids":["https://openalex.org/I73613424"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005009278","display_name":"Kohei Nogita","orcid":"https://orcid.org/0000-0002-7578-3113","observed_orcids":["https://orcid.org/0000-0002-7578-3113"]},"institutions":[{"id":"https://openalex.org/I73613424","display_name":"National Institute of Advanced Industrial Science and Technology","ror":"https://ror.org/01703db54","country_code":"JP","type":"government","lineage":["https://openalex.org/I73613424"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kohei Nogita","raw_affiliation_strings":["Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan, 305-8577"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan, 305-8577","institution_ids":["https://openalex.org/I73613424"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070143024","display_name":"Katsuya Maruyama","orcid":"https://orcid.org/0000-0003-0662-5987","observed_orcids":["https://orcid.org/0000-0003-0662-5987"]},"institutions":[{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Katsuya Maruyama","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","institution_ids":["https://openalex.org/I74801974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5021174309","display_name":"Koh Takeuchi","orcid":"https://orcid.org/0000-0002-6227-4627","observed_orcids":["https://orcid.org/0000-0002-6227-4627"]},"institutions":[{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Koh Takeuchi","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","institution_ids":["https://openalex.org/I74801974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088288669","display_name":"Motomu Kanai","orcid":"https://orcid.org/0000-0003-1977-7648","observed_orcids":["https://orcid.org/0000-0003-1977-7648"]},"institutions":[{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Motomu Kanai","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","institution_ids":["https://openalex.org/I74801974"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5067303784","display_name":"Kounosuke Oisaki","orcid":"https://orcid.org/0000-0002-0499-8168","observed_orcids":["https://orcid.org/0000-0002-0499-8168"]},"institutions":[{"id":"https://openalex.org/I73613424","display_name":"National Institute of Advanced Industrial Science and Technology","ror":"https://ror.org/01703db54","country_code":"JP","type":"government","lineage":["https://openalex.org/I73613424"]},{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kounosuke Oisaki","raw_affiliation_strings":["Catalytic Chemistry Research Institute (CCRI), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5-2, 1-1-1 Higashi, Tsukuba, Ibaraki, Japan, 305-8565","Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan, 305-8577"],"raw_orcid":"https://orcid.org/0000-0002-0499-8168","affiliations":[{"raw_affiliation_string":"Catalytic Chemistry Research Institute (CCRI), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5-2, 1-1-1 Higashi, Tsukuba, Ibaraki, Japan, 305-8565","institution_ids":["https://openalex.org/I73613424"]},{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033","institution_ids":["https://openalex.org/I74801974"]},{"raw_affiliation_string":"Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan, 305-8577","institution_ids":["https://openalex.org/I73613424"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"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/T10911","display_name":"Chemical Synthesis and Analysis","score":0.9994999766349792,"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/T10911","display_name":"Chemical Synthesis and Analysis","score":0.9994999766349792,"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/T10044","display_name":"Protein Structure and Dynamics","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13326","display_name":"Biochemical and Structural Characterization","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/late-stage-peptide-modification","display_name":"late-stage peptide modification","score":0.7490000128746033},{"id":"https://openalex.org/keywords/amide-nitrogen","display_name":"amide nitrogen","score":0.47099998593330383},{"id":"https://openalex.org/keywords/conformational-restriction","display_name":"conformational restriction","score":0.7039999961853027},{"id":"https://openalex.org/keywords/peptide-conformation","display_name":"peptide conformation","score":0.4819999933242798},{"id":"https://openalex.org/keywords/protease-resistance","display_name":"protease resistance","score":0.6420000195503235},{"id":"https://openalex.org/keywords/beta-hairpin-peptides","display_name":"\u03b2-hairpin peptides","score":0.777999997138977},{"id":"https://openalex.org/keywords/chemical-mutagenesis","display_name":"chemical mutagenesis","score":0.753000020980835},{"id":"https://openalex.org/keywords/unnatural-amino-acids","display_name":"unnatural amino acids","score":0.6449999809265137}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.800599992275238},{"id":"https://openalex.org/C2781338088","wikidata":"https://www.wikidata.org/wiki/Q903495","display_name":"Residue (chemistry)","level":2,"score":0.6621999740600586},{"id":"https://openalex.org/C2776165026","wikidata":"https://www.wikidata.org/wiki/Q188017","display_name":"Tyrosine","level":2,"score":0.6517999768257141},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.6270999908447266},{"id":"https://openalex.org/C60984968","wikidata":"https://www.wikidata.org/wiki/Q389172","display_name":"Cyclic peptide","level":3,"score":0.6003000140190125},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5411999821662903},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.46810001134872437},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.4677000045776367},{"id":"https://openalex.org/C204921945","wikidata":"https://www.wikidata.org/wiki/Q899689","display_name":"Side chain","level":3,"score":0.46239998936653137},{"id":"https://openalex.org/C75079739","wikidata":"https://www.wikidata.org/wiki/Q1571801","display_name":"Intramolecular force","level":2,"score":0.43479999899864197},{"id":"https://openalex.org/C2778530040","wikidata":"https://www.wikidata.org/wiki/Q1937315","display_name":"Helix (gastropod)","level":3,"score":0.3889000117778778},{"id":"https://openalex.org/C16318435","wikidata":"https://www.wikidata.org/wiki/Q149299","display_name":"Mutagenesis","level":4,"score":0.3634999990463257},{"id":"https://openalex.org/C2778439535","wikidata":"https://www.wikidata.org/wiki/Q188777","display_name":"Amide","level":2,"score":0.3474000096321106},{"id":"https://openalex.org/C2776568683","wikidata":"https://www.wikidata.org/wiki/Q23005640","display_name":"Moiety","level":2,"score":0.3422999978065491},{"id":"https://openalex.org/C2779809887","wikidata":"https://www.wikidata.org/wiki/Q14864278","display_name":"Peptide synthesis","level":3,"score":0.3411000072956085},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.31450000405311584},{"id":"https://openalex.org/C109300003","wikidata":"https://www.wikidata.org/wiki/Q4384651","display_name":"Polyproline helix","level":3,"score":0.3009999990463257},{"id":"https://openalex.org/C2779201268","wikidata":"https://www.wikidata.org/wiki/Q186474","display_name":"Cysteine","level":3,"score":0.2793000042438507},{"id":"https://openalex.org/C2777431362","wikidata":"https://www.wikidata.org/wiki/Q170545","display_name":"Phenylalanine","level":3,"score":0.26489999890327454},{"id":"https://openalex.org/C184651966","wikidata":"https://www.wikidata.org/wiki/Q906356","display_name":"Aqueous solution","level":2,"score":0.2551000118255615}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.26434/chemrxiv.15008909/v1","doi":"https://doi.org/10.26434/chemrxiv.15008909/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15008909/v1","pdf_url":null,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.26434/chemrxiv.15008909/v1","doi":"https://doi.org/10.26434/chemrxiv.15008909/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15008909/v1","pdf_url":null,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2567228404","https://openalex.org/W2049973341","https://openalex.org/W2064144150","https://openalex.org/W2587918761","https://openalex.org/W4417455255","https://openalex.org/W6927256447","https://openalex.org/W1511281499","https://openalex.org/W4417332433","https://openalex.org/W2322841128","https://openalex.org/W2011718452"],"abstract_inverted_index":{"The":[0],"biological":[1],"and":[2,23,92,113,192],"physicochemical":[3],"properties":[4],"of":[5,48,65,105,127,195],"peptides":[6],"are":[7],"strongly":[8],"influenced":[9],"by":[10,53],"their":[11],"backbone":[12,67,121,163,179],"conformations.":[13],"However,":[14],"installing":[15],"conformationally":[16],"restricting":[17],"units":[18],"generally":[19],"requires":[20],"peptide":[21,82,135,171],"redesign":[22],"resynthesis":[24],"using":[25,131],"noncanonical":[26],"amino":[27,40],"acids.":[28],"Here,":[29],"we":[30],"report":[31],"a":[32,38,44,58,76,132,150,157,162,184],"late-stage":[33,190],"backbone-editing":[34],"method":[35,148],"that":[36,117,138,154],"converts":[37,156],"native":[39,158],"acid":[41],"residue":[42,74,160],"into":[43,75,161],"proline-mimetic":[45,78,120,140],"structure.":[46],"Treatment":[47],"the":[49,66,72,81,103,106,118,123,128,139,169,189],"dearomatized":[50],"intermediate":[51],"generated":[52],"tyrosine-selective":[54],"oxime":[55],"conjugation":[56],"in":[57],"basic":[59],"aqueous":[60,90],"buffer":[61],"induced":[62],"intramolecular":[63],"1,4-addition":[64],"amide":[68],"nitrogen,":[69],"thereby":[70],"converting":[71],"tyrosine":[73,159],"cyclic":[77],"unit":[79,166],"within":[80],"backbone.":[83],"This":[84,147],"transformation":[85],"proceeded":[86],"efficiently":[87],"under":[88],"mild":[89],"conditions":[91],"was":[93],"applicable":[94],"to":[95,144],"several":[96],"bioactive":[97],"peptides.":[98,196],"Multidimensional":[99],"NMR":[100],"analyses":[101],"established":[102],"structures":[104],"resulting":[107],"products,":[108],"while":[109],"conventional":[110],"molecular":[111],"dynamics":[112],"REST2":[114],"simulations":[115],"demonstrated":[116,137],"installed":[119],"reduced":[122],"local":[124],"conformational":[125,164,191],"freedom":[126],"peptide.":[129],"Evaluation":[130],"\u03b2-hairpin":[133],"model":[134],"further":[136],"structure":[141],"enhanced":[142],"resistance":[143],"proteolytic":[145],"degradation.":[146],"constitutes":[149],"chemical":[151],"mutagenesis":[152],"strategy":[153,182],"directly":[155],"control":[165],"without":[167],"reconstructing":[168],"parent":[170],"sequence.":[172],"By":[173],"connecting":[174],"residue-selective":[175],"side-chain":[176],"modification":[177],"with":[178],"editing,":[180],"this":[181],"provides":[183],"new":[185],"design":[186],"concept":[187],"for":[188],"functional":[193],"diversification":[194]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-17T00:00:00"}