PXD045387 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction |
Description | The chemical bioconjugation of proteins has seen tremendous applications in the past decades, with the booming of antibody-drug conjugates and their use in oncology. While genetic engineering has permitted to produce bespoke proteins featuring key (un-)natural amino acid residues poised for site-selective modifications, the conjugation of native proteins is riddled with selectivity issues. Chemoselective strategies are plentiful and enable the precise modification of virtually any residue with a reactive side-chain; site-selective methods are less common and usually most effective on small and medium-sized proteins. In this context, we studied the application of the Ugi multicomponent reaction for the site-selective conjugation of amine and carboxylate groups on proteins, and antibodies in particular. Through an in-depth mechanistic methodology work supported by peptide mapping studies, we managed to develop a set of conditions allowing the highly selective modification of antibodies bearing N-terminal glutamate and aspartate residues. We demonstrated that this strategy did not alter their affinity toward their target antigen and produced an antibody-drug conjugate with subnanomolar potency. Excitingly, we showed that the high site selectivity of our strategy was maintained on other protein formats, especially on anticalins, for which directed mutagenesis helped to highlight the key importance of a single lysine residue. |
HostingRepository | PRIDE |
AnnounceDate | 2024-09-09 |
AnnouncementXML | Submission_2024-09-09_02:08:41.995.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hélène Diemer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-09-14 06:37:45 | ID requested | |
⏵ 1 | 2024-09-09 02:08:42 | announced | |
Publication List
Keyword List
submitter keyword: Biomolecule |
site conjugation |
chemical biology |
peptide mapping; |
Contact List
Dr Sarah Cianferani |
contact affiliation | Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg,CNRS, IPHC UMR 7178, 67087 Strasbourg,France |
contact email | sarah.cianferani@unistra.fr |
lab head | |
Hélène Diemer |
contact affiliation | LSMBO |
contact email | hdiemer@unistra.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045387
- Label: PRIDE project
- Name: Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction