A New Strategy for the Preparation of Peptide-Targeted Technetium and Rhenium Radiopharmaceuticals. The Automated Solid-Phase Synthesis, Characterization, Labeling, and Screening of a Peptide-Ligand L
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- 作者：Karin A. Stephenson ; Sangeeta Ray Banerjee ; Oyebola O. Sogbein ; Murali K. Levadala ; Nicole McFarlane ; Douglas R. Boreham ; Kevin P. Maresca ; John W. Babich ; Jon Zubieta ; and John F. Valliant
- 刊名：Bioconjugate Chemistry
- 出版年：2005
- 出版时间：September 2005
- 年：2005
- 卷：16
- 期：5
- 页码：1189 - 1195
- 全文大小：169K
- 年卷期：v.16,no.5(September 2005)
- ISSN：1520-4812
文摘
A new solid-phase synthetic methodology was developed that enables libraries of peptide-based Tc(I)/Re(I) radiopharmaceuticals to be prepared using a conventional automated peptide synthesizer.Through the use of a tridentate ligand derived from N-
-Fmoc-L-lysine, which we refer to as a singleamino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl,isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formylpeptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell formaton an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptidewere isolated in high purity without HPLC purification. After characterization, the library componentswere screened for their affinity for the FPR receptor using flow cytometry where the Kd values werefound to be in the low micromolar range (0.5-3.0 
M). Compound 5j was subsequently labeled with99mTc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purificationprocedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology thatwas used to construct the library. The work reported here is a rare example of a method by whichlibraries of peptide-ligand conjugates and their rhenium complexes can be prepared.
-Fmoc-L-lysine, which we refer to as a singleamino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl,isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formylpeptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell formaton an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptidewere isolated in high purity without HPLC purification. After characterization, the library componentswere screened for their affinity for the FPR receptor using flow cytometry where the Kd values werefound to be in the low micromolar range (0.5-3.0 M). Compound 5j was subsequently labeled with99mTc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purificationprocedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology thatwas used to construct the library. The work reported here is a rare example of a method by whichlibraries of peptide-ligand conjugates and their rhenium complexes can be prepared.