Convenient Solid-Phase Synthesis of Diethylenetriaminepenta-Acetic Acid (DTPA)– Conjugated Cyclic RGD Peptide Analogues
| Autor: | Martin L. Campbell, John S. McMurray, Wei Wang, Chun Li, Qingping Wu |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Integrins
Cancer Research Time Factors Stereochemistry animal diseases Amino Acid Motifs Mice Nude Peptide Conjugated system Mass Spectrometry Inhibitory Concentration 50 Mice Solid-phase synthesis In vivo Cell Line Tumor Animals Humans Radiology Nuclear Medicine and imaging Melanoma Pharmacology chemistry.chemical_classification Integrin alphaVbeta3 Dose-Response Relationship Drug organic chemicals General Medicine Pentetic Acid respiratory system Fluoresceins Cyclic peptide In vitro Models Chemical Oncology chemistry Biochemistry cardiovascular system Peptides Oligopeptides Neoplasm Transplantation circulatory and respiratory physiology Conjugate |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 20:547-556 |
| ISSN: | 1557-8852 1084-9785 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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