Cyclization of peptides through a urea bond: application to the Arg-Gly-Asp tripeptide.
Various synthetic cyclopeptides bind different cellular proteins with high affinity and specificity. In this study, we designed a new series of cyclic tetrapeptides containing the RGD sequence, a ligand for the alpha(v)beta(3) integrin receptor, in which the ring closure was performed through a urea bond between the alpha-amino group of the peptide and either the alpha- or the epsilon-amino group of an additional lysine. Interestingly, we showed that the urea-closed peptide had a higher affinity for alpha(v)beta(3) receptors than a reference pentacyclopeptide. Moreover, the synthetic strategy allows coupling of the resulting cyclic tetrapeptide through the carboxylic acid moiety of its lysine residue to fluorescent molecules or drugs. In addition, this strategy could be easily adapted for the cyclization of any other peptides.
Schmidt
Julien
J
Institut de Recherche en Cancérologie de Montpellier, Université Montpellier1, Montpellier, France.
Garambois
Véronique
V
Rocheblave
Luc
L
Martinez
Jean
J
Pèlegrin
André
A
Cavelier
Florine
F
Vivès
Eric
E
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003500:Cyclization; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D014508:Urea / Q000737:chemistry*
D020533:Angiogenesis Inhibitors; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D014508:Urea