PDF herunterladen
Synfacts 2023; 19(07): 0721
DOI: 10.1055/s-0042-1751934
Innovative Drug Discovery and Development

Controlling Protein Activity with a Carboxyl Group Cage

Rezensent(en):
Dirk Trauner
,
Tongil Ko
Petri YD, Gutierrez CS, Raines RT. * Massachusetts Institute of Technology, Cambridge, USA
Chemoselective Caging of Carboxyl Groups for On-Demand Protein Activation with Small Molecules.

Angew. Chem. Int. Ed. 2023;
62: e202215614
DOI: 10.1002/anie.202215614.
CrossrefPubMedGoogle Scholar
› Weitere Informationen
 
 als PDF herunterladen Lizenzen und Reprints

Key words

cage - 1,3-dipolar cycloaddition - Staudinger reduction

Significance

Amino acid cages are valuable chemical tools for controlling the activity and interactions of proteins. Protein cages have been primarily designed for Lys, Tyr, and Sec amino acids. In this study, the authors expand this toolbox by developing diazo-based compound 1 that can selectively cage solvent-exposed amino acids containing carboxyl groups. The caged residues can be released, in a traceless fashion, with two small-molecule triggers.


#

Comment

To demonstrate the utility of their tool, the authors caged lysozyme (Lyz), which has a catalytic Glu35 with elevated pK a. Lyz-1 shows severely reduced catalytic activity, which can be recovered through the addition of commercially available 2-DPBA and TCO-OH. The addition of these two small-molecule triggers leads to uncaging to the wild-type Lyz enzyme.


#
#

Publikationsverlauf

Artikel online veröffentlicht:
16. Juni 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


   Lizenzen und Reprints