Design, synthesis and glycosidase inhibition of DAB derivatives with C-4 peptide and dipeptide branches

A series of DAB-peptide and DAB-dipeptide derivatives were synthesized from D-tartrate-derived nitrone 18. The DAB peptides 16 are derivatives of trans,trans-3,4-dihydroxy-L-proline. Glycosidase inhibition assay found four of them to be weak and selective bovine liver β-galactosidase inhibitors, and the C-2' methyl substituted compound 23b showed the most potent β-galactosidase inhibition (IC₅₀ = 0.66 μM). Molecular docking studies revealed different docking modes of compound 23b compared to those of other DAB-peptides, and partial similarity of compound 23b to DGJ.