[Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides

Native chemical ligation (NCL) ligates two unprotected peptides in an aqueous buffer. One of the fragments features a C-terminal α-thioester functional group, and the second bears an N-terminal cysteine. The reaction mechanism depicts two steps: an intermolecular thiol-thioester exchange resulting i...

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Detalles Bibliográficos
Autores: Sánchez-Campillo, Iván, Blanco-Canosa, Juan Bautista
Tipo de recurso: conjunto de datos
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/383778
Acceso en línea:http://hdl.handle.net/10261/383778
https://digital.csic.es/handle/10261/371685
Access Level:acceso abierto
Palabra clave:Thioesters
Chemical protein synthesis
Native chemical ligation
Peptides
Selenoesters
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
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oai_identifier_str oai:digital.csic.es:10261/383778
network_acronym_str ES
network_name_str España
repository_id_str
spelling [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester PeptidesSánchez-Campillo, IvánBlanco-Canosa, Juan BautistaThioestersChemical protein synthesisNative chemical ligationPeptidesSelenoestershttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all agesNative chemical ligation (NCL) ligates two unprotected peptides in an aqueous buffer. One of the fragments features a C-terminal α-thioester functional group, and the second bears an N-terminal cysteine. The reaction mechanism depicts two steps: an intermolecular thiol-thioester exchange resulting in a transient thioester, followed by an intramolecular S-to-N acyl shift to yield the final native peptide bond. Although this mechanism is well established, the direct observation of the transient thioester has been elusive because the fast intramolecular rearrangement prevents its accumulation. Here, the use of α-selenoester peptides allows a faster first reaction and an early buildup of the intermediate, enabling its quantification and the kinetic monitoring of the first and second steps. The results show a correlation between the steric hindrance in the α-thioester residue and the rearrangement rate. In bulky residues, the S-to-N acyl shift has a significant contribution to the overall reaction rate. This is particularly notable for valine and likely for other similar β-branched amino acids.This work has been funded by the Spanish Ministerio de Ciencia, Innovación y Universidades (PDI2021-128902OB-I00). I. S.-C. acknowledges AGAUR (Generalitat de Catalunya) for a fellowship (2021 FI-B 00142).Peer reviewedAmerican Chemical Society0000-0002-8666-80650000-0001-5738-6993Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/datasethttp://purl.org/coar/resource_type/c_ddb1http://hdl.handle.net/10261/383778https://digital.csic.es/handle/10261/371685reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésJACS AuKinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester PeptidesSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3837782026-05-22T06:33:51Z
dc.title.none.fl_str_mv [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
title [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
spellingShingle [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
Sánchez-Campillo, Iván
Thioesters
Chemical protein synthesis
Native chemical ligation
Peptides
Selenoesters
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
title_short [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
title_full [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
title_fullStr [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
title_full_unstemmed [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
title_sort [Dataset] Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
dc.creator.none.fl_str_mv Sánchez-Campillo, Iván
Blanco-Canosa, Juan Bautista
author Sánchez-Campillo, Iván
author_facet Sánchez-Campillo, Iván
Blanco-Canosa, Juan Bautista
author_role author
author2 Blanco-Canosa, Juan Bautista
author2_role author
dc.contributor.none.fl_str_mv 0000-0002-8666-8065
0000-0001-5738-6993
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Thioesters
Chemical protein synthesis
Native chemical ligation
Peptides
Selenoesters
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
topic Thioesters
Chemical protein synthesis
Native chemical ligation
Peptides
Selenoesters
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
description Native chemical ligation (NCL) ligates two unprotected peptides in an aqueous buffer. One of the fragments features a C-terminal α-thioester functional group, and the second bears an N-terminal cysteine. The reaction mechanism depicts two steps: an intermolecular thiol-thioester exchange resulting in a transient thioester, followed by an intramolecular S-to-N acyl shift to yield the final native peptide bond. Although this mechanism is well established, the direct observation of the transient thioester has been elusive because the fast intramolecular rearrangement prevents its accumulation. Here, the use of α-selenoester peptides allows a faster first reaction and an early buildup of the intermediate, enabling its quantification and the kinetic monitoring of the first and second steps. The results show a correlation between the steric hindrance in the α-thioester residue and the rearrangement rate. In bulky residues, the S-to-N acyl shift has a significant contribution to the overall reaction rate. This is particularly notable for valine and likely for other similar β-branched amino acids.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/dataset
http://purl.org/coar/resource_type/c_ddb1
format dataset
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/383778
https://digital.csic.es/handle/10261/371685
url http://hdl.handle.net/10261/383778
https://digital.csic.es/handle/10261/371685
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv JACS Au
Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410767799844864
score 15,81155

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