Constraining and Modifying Peptides Using Pd-Mediated Cysteine Allylation.
Chembiochem
; 24(13): e202300098, 2023 07 03.
Article
em En
| MEDLINE
| ID: mdl-36917494
ABSTRACT
Over the past decades, several strategies for inducing and stabilizing secondary structure formation in peptides have been developed to increase their proteolytic stability and their binding affinity to specific interaction partners. Here, we report how our recently introduced chemoselective Pd-catalyzed cysteine allylation reaction can be extended to stapling and how the resulting alkene-containing staples themselves can be further modified to introduce additional probes into such stabilized peptides. The latter is demonstrated by introducing a fluorophore as well as a PEG moiety into different stapled peptides using bioorthogonal thiol-ene and Diels-Alder reactions. Furthermore, we investigated structural implications of our allyl staples when used to replace conformationally relevant disulfide bridges. To this end, we chose a selective binder of integrin α3 ß1 (LXY3), which is only active in its cyclic disulfide form. We replaced the disulfide bridge by different stapling reagents in order to increase stability and binding affinity towards integrin α3 ß1 .
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Cisteína
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article