3 research outputs found
Selection of Effective HTRA3 Activators Using Combinatorial Chemistry
No full textHerein, we report selection, synthesis,
and enzymatic evaluation
of a peptidomimetic library able to increase proteolytic activity
of HtrA3 (high temperature requirement A) protease. Iterative deconvolution
in solution of synthesized modified pentapeptides yielded two potent
HtrA3 activators acting in the micromolar range (HCOO-CH<sub>2</sub>O-C<sub>6</sub>H<sub>4</sub>-OCH<sub>2</sub>-CO-Tyr-Asn-Phe-His-Asn-OH
and HCOO-CH<sub>2</sub>O-C<sub>6</sub>H<sub>4</sub>-OCH<sub>2</sub>-CO-Tyr-Asn-Phe-His-Glu-OH). Both compounds increased proteolysis
of an artificial HtrA3 substrate over 40-fold in a selective manner.
On the basis of molecular modeling, the selected compounds bind strongly
to the PDZ domain
