Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/134190 |
Resumo: | SFRH//BD/ 90644/2012 SFRH/ BPD/114848/2016 Project No. 022161 FA9550-19-1-0111 RF19-4862 |
| id |
RCAP_089529998407d083b8e02c04fc04a51f |
|---|---|
| oai_identifier_str |
oai:run.unl.pt:10362/134190 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivityChemistry(all)SFRH//BD/ 90644/2012 SFRH/ BPD/114848/2016 Project No. 022161 FA9550-19-1-0111 RF19-4862We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH2(P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state withKD= 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY through the KVYF terminus and this binding event disrupts the assembled structure. In absence of the target micellar aggregate, P7 was further found to dynamically alternate between multiple conformations, with a preferred hairpin-like conformation that was shown to contribute to supramolecular ligand binding. Three identified phages presented appreciable binding, and two showed to catalyze the hydrolysis of a modelpara-nitro phenol phosphate substrate, with P7 demonstrating conformation-dependent activity with a modestkcat/KM= 4 ± 0.3 × 10−4M−1s−1UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaCENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N)DCM - Departamento de Ciência dos MateriaisRUNPina, Ana S.Morgado, LeonorDuncan, Krystyna L.Carvalho, SaraCarvalho, Henrique F.Barbosa, Arménio J. M.de P. Mariz, BeatrizMoreira, Inês P.Kalafatovic, DanielaMorais Faustino, Bruno M.Narang, VishalWang, TongPappas, Charalampos G.Ferreira, IsabelRoque, Ana Cecília AfonsoUlijn, Rein V.2022-03-09T23:24:53Z2022-01-072022-01-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://hdl.handle.net/10362/134190eng2041-6520PURE: 36729149https://doi.org/10.1039/d1sc04420finfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:12:37Zoai:run.unl.pt:10362/134190Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:48:00.602920Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| title |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| spellingShingle |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity Pina, Ana S. Chemistry(all) |
| title_short |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| title_full |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| title_fullStr |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| title_full_unstemmed |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| title_sort |
Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity |
| author |
Pina, Ana S. |
| author_facet |
Pina, Ana S. Morgado, Leonor Duncan, Krystyna L. Carvalho, Sara Carvalho, Henrique F. Barbosa, Arménio J. M. de P. Mariz, Beatriz Moreira, Inês P. Kalafatovic, Daniela Morais Faustino, Bruno M. Narang, Vishal Wang, Tong Pappas, Charalampos G. Ferreira, Isabel Roque, Ana Cecília Afonso Ulijn, Rein V. |
| author_role |
author |
| author2 |
Morgado, Leonor Duncan, Krystyna L. Carvalho, Sara Carvalho, Henrique F. Barbosa, Arménio J. M. de P. Mariz, Beatriz Moreira, Inês P. Kalafatovic, Daniela Morais Faustino, Bruno M. Narang, Vishal Wang, Tong Pappas, Charalampos G. Ferreira, Isabel Roque, Ana Cecília Afonso Ulijn, Rein V. |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
UCIBIO - Applied Molecular Biosciences Unit DQ - Departamento de Química CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N) DCM - Departamento de Ciência dos Materiais RUN |
| dc.contributor.author.fl_str_mv |
Pina, Ana S. Morgado, Leonor Duncan, Krystyna L. Carvalho, Sara Carvalho, Henrique F. Barbosa, Arménio J. M. de P. Mariz, Beatriz Moreira, Inês P. Kalafatovic, Daniela Morais Faustino, Bruno M. Narang, Vishal Wang, Tong Pappas, Charalampos G. Ferreira, Isabel Roque, Ana Cecília Afonso Ulijn, Rein V. |
| dc.subject.por.fl_str_mv |
Chemistry(all) |
| topic |
Chemistry(all) |
| description |
SFRH//BD/ 90644/2012 SFRH/ BPD/114848/2016 Project No. 022161 FA9550-19-1-0111 RF19-4862 |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-03-09T23:24:53Z 2022-01-07 2022-01-07T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/134190 |
| url |
http://hdl.handle.net/10362/134190 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
2041-6520 PURE: 36729149 https://doi.org/10.1039/d1sc04420f |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
8 application/pdf |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| repository.mail.fl_str_mv |
|
| _version_ |
1799138081613283328 |