Title:	Amplification of enzyme activity with small molecule catalysts
DNr:	Berzelius-2025-204
Project Type:	LiU Berzelius
Principal Investigator:	Thomas Helleday <thomas.helleday@ki.se>
Affiliation:	Karolinska Institutet
Duration:	2025-06-26 – 2026-01-01
Classification:	10610
Homepage:	https://helleday.org/
Keywords:

Abstract

Small molecules and peptides are an attractive modality for modification of enzymatic activity, due to their high-affinity binding combined with their relatively small size. However, many designed molecules are not permeable through the cell membrane, so they cannot reach 'undruggable' intracellular targets. In this project we propose to design molecules against specific targets using existing ML methods, evaluate their cell permeability in the lab, then use this data to integrate constraints into design methods. This will facilitate the design of membrane-permeable molecules that can interfere with enzymatic activity of intracellular targets.