PXD045387-1

PXD045387 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-14 06:37:45	ID requested
⏵ 1	2024-09-09 02:08:42	announced

10.1002/CHEM.202303242;

submitter keyword: Biomolecule

site conjugation

chemical biology

peptide mapping;

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD045387

PRIDE project URI

• PRIDE
  1. PXD045387
     1. Label: PRIDE project
     2. Name: Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction