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Controlling γ‐Peptide Helicity with Stereoselective Fluorination
Author(s) -
Lawer Aggie,
Hunter Luke
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001619
Subject(s) - chemistry , stereoselectivity , helicity , helix (gastropod) , stereochemistry , peptide , amino acid , molecule , combinatorial chemistry , organic chemistry , biochemistry , catalysis , ecology , physics , particle physics , snail , biology
Peptides that are composed of backbone‐extended amino acids can adopt conformations resembling natural α‐peptidic motifs, making them promising scaffolds for biological and medicinal chemistry. In order to unlock the full potential of this class of molecules, the ability to control their secondary structures is essential. Here we show that stereoselective fluorination can be harnessed as a tool for influencing the helical character of a γ‐hexapeptide. Fluorination is shown to either stabilize or disrupt the 9‐helical conformation depending on the C−F stereochemistry, and fluorination also sets the handedness of the helix. These results provide fundamental knowledge that could expedite the future development of backbone‐extended peptides for medicinal applications.