Fluorinated pseudopeptide analogues of the neuropeptide 26RFa: synthesis, biological, and structural studies.
A series of four fluorinated dipeptide analogues each containing a fluoro-olefin moiety as peptide bond surrogate has been designed and synthesized. These motifs have been successfully introduced into the bioactive C-terminal heptapeptide of the neuropeptide 26RFa by conventional SPPS. We then evaluated the ability of the generated pseudopeptides to increase [Ca²⁺](i) in GPR103-transfected cells. For these fluorinated analogues, greater stability in human serum was observed. Their conformations were also investigated, leading to the valuable identification of differences depending on the position of the fluoro-olefin moiety in the sequence.
UMR 6014 COBRA, INSA and University of Rouen, IRCOF, 1 rue Tesnière, 76130 Mont-Saint-Aignan (France).
Camille
C
Pierry
Samuel
S
Couve-Bonnaire
Laure
L
Guilhaudis
Cindy
C
Neveu
Amélie
A
Marotte
Benjamin
B
Lefranc
Dominique
D
Cahard
Isabelle
I
Ségalas-Milazzo
Jérôme
J
Leprince
Xavier
X
Pannecoucke
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D003412:Cricetulus; D005461:Fluorine / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D015394:Molecular Structure; D009479:Neuropeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D009479:Neuropeptides; D010455:Peptides; C480638:prepro-26RFa protein, human; D005461:Fluorine; D002118:Calcium
biological evaluation; conformation analysis; fluoro-olefins; peptides; pseudopeptides