title: Convenient solid-phase synthesis of diethylenetriaminepenta-acetic acid (DTPA)- conjugated cyclic RGD peptide analogues.
abstract: 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.
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: John S
authors.initials: JS
authors.lastname: McMurray
authors.forename: Qingping
authors.initials: Q
authors.lastname: Wu
authors.forename: Martin L
authors.initials: ML
authors.lastname: Campbell
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: 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
chemical_list: D005452:Fluoresceins; D016023:Integrins; D009842:Oligopeptides; D010455:Peptides; C024098:6-carboxyfluorescein; C047981:arginyl-glycyl-aspartic acid; D004369:Pentetic Acid