Synthesis and biological evaluation of lipophilic Ca1a2L analogues as potential bisubstrate inhibitors of protein:geranylgeranyl transferase-1 Original Research Article

Ca1a2L analogues, having the central dipeptide a1a2 replaced by a sugar amino acid, were provided at the N-terminal end directly or via a spacer with a lipid. The inhibitory potency toward PGGT-1 of the set of lipophilic Ca1a2L analogues was improved in comparison with the original analogues, 1 and 2. The most potent inhibitors, 39 and 40, were found to inhibit PGGT-1 with an IC50-value of 12.7 and 12.3 μM, respectively, which is a 6-fold improvement over the corresponding analogue 1.