Syntheses of some α-cyclic tripeptides as potential inhibitors for HMG-CoA Reductase.
α-Cyclic tripeptides (CtPs) are the most rigid members of the cyclic peptide family. However, due to their synthetic difficulty, biological activity has remained undisclosed. The incorporation of side-chain-protected natural amino acids into functional CtPs was performed to explore the potential biological functions. Several novel CtPs that consist of protected serine (S(Bn)) and/or glutamate (E(OBn)) were prepared from corresponding linear tripeptides by chemical synthesis. There is a strong possibility for CtPs that contain 3 phenyl groups to correlate with atorvastatin structure. The binding effects in human HMG-CoA reductase (hHMGR) activities were first evaluated by molecular docking. High docking scores were received with these CtPs for enzyme. Therefore, enzymatic assays were carried out and the compound cyclo(S(Bn))3 was indeed able to moderately inhibit hHMGR (IC50 = 110 μM).
Department of Chemistry, National Dong-Hwa University, Hualien, 974, Taiwan, ROC, cpapu2000@yahoo.com.
Subrata
S
Chakraborty
Shih-Hung
SH
Lin
David
D
Shiuan
Dar-Fu
DF
Tai
D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012694:Serine / Q000737:chemistry
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010456:Peptides, Cyclic; D018698:Glutamic Acid; D012694:Serine; D006903:Hydroxymethylglutaryl CoA Reductases