Orthogonally Protected Artificial Amino Acid as Tripod Ligand for Automated Peptide Synthesis and Labeling with [99mTc(OH2)3(CO)3]+

1,2-Diamino-propionic acid (Dap) is a very strong chelator for the [99mTc(CO)3]+ core, yielding small and hydrophilic complexes. We prepared the lysine based Dap derivative l-Lys(Dap) in which the e-NH2 group was replaced by the tripod through conjugation to its α-carbon. The synthetic strategy produced an orthogonally protected bifunctional chelator (BFC). The -NH2 group of the α-amino acid portion is Fmoc- and the -NH2 of Dap are Boc-protected. Fmoc-l-Lys(Dap(Boc)) was either conjugated to the N- and C-terminus of bombesin BBN(7–14) or integrated into the sequence using solid-phase peptide synthesis (SPPS). We also replaced the native lysine in a cyclic RGD peptide with l-Lys(Dap). For all peptides, quantitative labeling with the [99mTc(CO)3]+ core at a 10 μM concentration in PBS buffer (pH = 7.4) was achieved. For comparison, the rhenium homologues were prepared from [Re(OH2)3(CO)3]+ and Lys(Dap)-BBN(7–14) or cyclo-(RGDyK(Dap)), respectively. Determination of integrin receptor binding showed low to med...