“Fluorine Effects” in Conformational Orchestration of α/β Hybrid Peptide with a 9‐membered Pseudo β‐Turn Motif

Abstract

Fluorine, the tiny robust atom, with its unique features has captured the attention of scientists in recent times, especially in drug discovery with its integration in small molecules, peptides, and proteins. However, studies to understand the ‘fluorine effects’ (‘fluorine magic’) on the conformation of molecules that follow ‘beyond the rule of 5’ are in the infancy yet significant in molecular design and function. For the first time, using short hybrid peptide sequence as an appropriate model, we examined the substitution effect (size, stereoelectronic effect, and hydrogen bonding) using X‐ray diffraction 2D‐NMR, and CD studies. The comparative study on their folding patterns with hydrogen‐substituted analogs can provide valuable insights into ‘flustrates’ fluorinated substrates’ design.