The structure-based design of constrained alpha-helical peptides derived from the viral suppressor of RNA silencing TAV2b is described. We observe that the introduction of two inter-side chain crosslinks provides peptides with increased alpha-helicity and protease stability. One of these modified peptides (B3) shows high affinity for different double-stranded RNA structures including a palindromic siRNA as well as microRNA-21 and its precursor pre-miR-21. Notably, B3 binding to pre-miR-21 inhibits Dicer processing in a biochemical assay. As a further characteristic this peptide also exhibits cellular entry.
20 12 03 SI ChemRxiv