Multimeric cyclic RGD peptides as potential tools for tumor targeting: solid-phase peptide synthesis and chemoselective oxime ligation.
The alpha v beta 3 integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Targeting this receptor may provide information about the receptor status of the tumor and enable specific therapeutic planning. Solid-phase peptide synthesis of multimeric cyclo(-RGDfE-)-peptides is described, which offer the possibility of enhanced integrin targeting due to polyvalency effects. These peptides contain an aminooxy group for versatile chemoselective oxime ligation. Conjugation with para-trimethylstannylbenzaldehyde results in a precursor for radioiododestannylation, which would allow them to be used as potential tools for targeting and imaging alpha v beta 3-expressing tumor cells. The conjugates were obtained in good yield without the need of a protection strategy and under mild conditions.
Thumshirn
Georgette
G
Institut für Organische Chemie und Biochemie, Technische Universität Munich, Lichtenbergstrasse 4, 85747 Garching, Germany.
Hersel
Ulrich
U
Goodman
Simon L
SL
Kessler
Horst
H
D000818:Animals; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D019096:Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010091:Oximes; D010456:Peptides, Cyclic; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid