Convenient solid-phase synthesis of diethylenetriaminepenta-acetic acid (DTPA)- conjugated cyclic RGD peptide analogues.
Solid-phase synthesis of radiometal chelator-conjugated peptides can facilitate the creation of radioactive peptide libraries to be utilized in high throughput in vivo screening of targeted nuclear-imaging agents. In this study, a new diethylenetriaminepentaacetic acid (DTPA) derivative, 1-(p-succinamidobenzyl)- DTPA penta-t-butyl ester [DTPA(But)(5)-Bz-NH-SA], and its precursor molecule, 1-(p-aminobenzyl)- DTPA penta-t-butyl ester (DTPA(But)(5)-Bz-NH(2)), were applied to the solid-phase synthesis of DTPA-conjugated cyclic peptides containing the Arg-Gly-Asp (RGD) motif with high efficiency. The resulting conjugates, DTPA-Bz-NH-SA-c(Lys-Arg-Gly-Asp-phe) [DTPA-Bz-NH-SA-c(KRGDf)] and DTPA-Bz-NHc( Glu-Arg-Gly-Asp-phe) [DTPA-Bz-NH-c(KRGDf)], demonstrated similar in vitro biologic activities as their corresponding parent peptides. (111)In-labeled, DTPA-conjugated RGD peptides showed selective binding to integrin alphavbeta3 in human melanoma M21 tumors grown in nude mice. Furthermore, (111)In-DTPABz- NH-c(ERGDf) showed lower retention in the liver and the kidney than (111)In-DTPA-Bz-NH-SAc( KRGDf) did, which contributed to higher target to nontarget ratio for (111)In-DTPA-Bz-NH-c(ERGDf). The method reported here can be extended to the construction of peptide libraries containing DTPA for high throughput in vitro and in vivo screening of molecularly targeted imaging agents.
Wang
Wei
W
Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
McMurray
John S
JS
Wu
Qingping
Q
Campbell
Martin L
ML
Li
Chun
C
D020816:Amino Acid Motifs; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D016023:Integrins / Q000737:chemistry; D013058:Mass Spectrometry; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*; D004369:Pentetic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D013997:Time Factors
D005452:Fluoresceins; D016023:Integrins; D009842:Oligopeptides; D010455:Peptides; C024098:6-carboxyfluorescein; C047981:arginyl-glycyl-aspartic acid; D004369:Pentetic Acid