Molecular Recognition by Zn(II)-Capped Dynamic Foldamers.

Two α-aminoisobutyric acid (Aib) foldamers bearing Zn(II)-chelating N-termini have been synthesized and compared with a reported Aib foldamer that has a bis(quinolinyl)/mono(pyridyl) cap (BQPA group). Replacement of the quinolinyl arms of the BQPA-capped foldamer with pyridyl gave a BPPA-capped foldamer, then further replacement of the linking pyridyl with a 1,2,3-triazole gave a BPTA-capped foldamer. Their ability to relay chiral information from carboxylate bound to Zn(II) at the N-terminus to a glycinamide-based NMR reporter of conformational preference at the C-terminus was measured.

Remote conformational responses to enantiomeric excess in carboxylate-binding dynamic foldamers.

A crystallographically characterised zinc(ii)-capped foldamer can sense the enantiomeric excess of scalemic carboxylate solutions, including those produced by enantioselective organocatalysis, and can relay this input signal along the foldamer body to a remote glycinamide group, which then provides an NMR spectroscopic output.

Bis-pyrene probes of foldamer conformation in solution and in phospholipid bilayers.

Exploring the detailed structural features of synthetic molecules in the membrane phase requires sensitive probes of conformation. Here we describe the design, synthesis and characterization of bis(pyrene) probes that report conformational changes in membrane-active dynamic foldamers. The probes were designed to distinguish between left-handed () and right-handed () screw-sense conformers of 3-helical α-aminoisobutyric acid (Aib) peptide foldamers, both in solution and in bilayer membranes.

Structure Activity Relationships of αv Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents.

Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program.