Sadruddin A
De-risking drug discovery of intracellular targeting peptides: screening strategies to eliminate false-positive hits
Non-specific promiscuous compounds can mislead researchers and waste significant resources. This phenomenon, though well-documented for small molecules, has not been widely explored for the peptide modality. Here, we demonstrate that two purported peptide-based KRas inhibitors, SAH-SOS1A and cyclorasin 9A5, exemplify false-positive molecules – both in terms of their binding affinities and cellular activities.
ReadIncorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties
Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus.
Read