RESUMO
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 [Ca²âº](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.
Assuntos
Flúor/química , Neuropeptídeos/química , Neuropeptídeos/metabolismo , Peptídeos/síntese química , Peptídeos/metabolismo , Animais , Células CHO , Cálcio/metabolismo , Cricetulus , Halogenação , Humanos , Estrutura Molecular , Neuropeptídeos/síntese química , Peptídeos/química , Relação Estrutura-AtividadeRESUMO
The addition reaction of organometallic reagents to N-(tert-butanesulfinyl)-α-fluoroenimines was studied. Depending of the nature of the organometallic species (Grignard reagents or zincate complexes), we were able to control the configuration of the newly created stereogenic centers in high yields with good to high diastereomeric ratios. The chiral ß-fluoro allylamines are key synthons toward the synthesis of fluorinated pseudopeptides bearing a fluoroolefin moiety as a peptide bond mimic.
Assuntos
Compostos de Flúor/síntese química , Iminas/química , Compostos Organometálicos/química , Compostos de Enxofre/química , Butanos/química , Estrutura Molecular , Peptídeos/síntese química , EstereoisomerismoRESUMO
The synthesis of fluorinated C-mannopeptides and their evaluation as E- and P-selectin inhibitors is described. These molecules are difluorinated analogues of CH(2)-glycopeptides already reported to act as sLe(x) mimics. The alpha and beta anomers of these CF(2)-glycopeptides have been prepared, as well as their 1-hydroxy analogues which were present in solution as an equilibrium mixture of alpha- and beta-pyranose and alpha- and beta-furanose forms. These molecules showed inhibitory activities comparable to their CH(2) counterparts with a moderate influence of the pseudo-anomeric center configuration.