Fig. 1: Motivation and design of our expanded Cbl derivative library.
From: Designing small molecules targeting a cryptic RNA binding site through base displacement
a, Chemical structure of standard Cbls with their corresponding β-axial groups shown. b, Cocrystal structure of the env8–OHCbl complex (PDB 4FRG)19. Left: global RNA architecture displayed as a cartoon, with nucleotides critical for recognition of the variable β-axial group shown in cyan (A68), green (A20) and yellow (G19); OHCbl is represented by magenta van der Waals spheres. Right: the ligand-binding pocket consists of a π-stacking network involving nucleotides G19–A20 and A20–A68 that is unimpeded by the small (–OH) β-axial group. c, Simplified chemical structures of previously characterized20 β-axial-modified Cbls 4–7 tested against env8. d, Reduction-free synthetic route25,26 to make Cbl derivatives from CNCbl using a variable alkyne. e, Overview of our expanded β-axial-modified Cbl library.
