Design, Synthesis and Docking of Linear and Hairpin‐Like Alpha Helix Mimetics Based on Alkoxylated Oligobenzamide

Abstract

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 α‐α “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.

Evolution in non-peptide α-helix mimetics on the road to effective protein-protein interaction modulators

“…(Figure 5) for potential receptor targets involved in virus infection, inflammation and immunomodulatory and neoplastic disease [65]. This new class of peptidomimetics could represent a starting point for the mimicry of high-ordered protein architectures.…”

Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era

“…146 Its structural stability is maintained by forming hydrogen bonds, so that the side chains have a relatively stable spatial orientation. 147 As reviewed by Slavokhotova et al, 148 members of alphahairpin family have been described in both mono and dicot groups, including species as Echinochloa crus-galli and Zea mays (both Poaceae, monocot), Fagopyrum esculentum (Polygonaceae, eudicot), and Stellaria media (Caryophyllaceae, eudicot). Several transcripts with α-hairpinin motif exhibit similarities to snakin/GASA genes and are sometimes positioned within this family.…”

“… 146 Its structural stability is maintained by forming hydrogen bonds, so that the side chains have a relatively stable spatial orientation. 147 …”