The influence of backbone fluorination on the helicity of α/γ-hybrid peptides
Alpesh Ramanlal Patel1, Aggie Lawer1, Mohan Bhadbhade2
1School of Chemistry, University of New South Wales (UNSW), Sydney, Australia. l.hunter@unsw.edu.au.
Abstract:
Peptides that are composed of an alternating pattern of α- and γ-amino acids are potentially valuable as metabolism-resistant bioactive agents. For optimal function, some kind of conformational restriction is usually required to either stabilize the dominant 12-helix, or else to divert the peptide away from this conformation in a controlled way. Herein, we explore stereoselective fluorination as a method for controlling the conformations of α/γ-hybrid peptides. We show through a combination of X-ray, NMR and CD analyses that fluorination can either stabilize or disrupt the 12-helix, depending on the fluorine stereochemistry. These findings could inform the ongoing development of diverse functional hybrid peptides.
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