Design, Synthesis And Docking Of Linear And Hairpin-Like Alpha Helix Mimetics Based On Alkoxylated Oligobenzamide

A series of 2-O-alkylated and 3-O-alkylated benzamide monomers and oligomers with various side chains were synthesized through an iterative (n+1) elongation approach. Based on these synthetic benzamide strands, a range of corresponding 2-O-alkylated and 3-O-alkylated oligobenzamide alpha-alpha "hairpin" mimetics were successfully prepared by different diacids reactions with amino-terminated benzamide oligomers or monomers in the presence of oxalyl chloride with the catalytic amount of DMF. Over fifty 2-O-alkylated and 3-O-alkylated oligobenzamide were synthesized to form alpha helix mimetics. A reverse docking was performed to screen the proteins of biological interest and identified potential biologically important proteins targeted by our molecules. A 2-O-alkylated oligobenzamide trimer ligand and a 2-O-alkylated oligobenzamide harpin ligand show high binding affinity to identified proteins with a good shape complementarity in their binding pockets.