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 with
99mTc(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.