1417177-28-6Relevant articles and documents
Orthogonally protected artificial amino acid as tripod ligand for automated peptide synthesis and labeling with [99mTc(OH2) 3(CO)3]+
Shen, Yunjun,Schottelius, Margret,Zelenka, Karel,De Simone, Mariarosaria,Pohle, Karolin,Kessler, Horst,Wester, Hans-Jürgen,Schmutz, Paul,Alberto, Roger
, p. 26 - 35 (2013/03/28)
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 ε-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 medium nanomolar affinities for various receptor subtypes. The IC50 of cyclo-(RGDyK(Dap[Re(CO)3])) for αvβ3 is 7.1 nM as compared to 3.1 nM for nonligated RGD derivative. Biodistribution studies in M21 melanoma bearing nude mice showed reasonable α vβ3-integrin specific tumor uptake. Altogether, orthogonally protected l-Lys(Dap) represents a highly versatile building block for integration in any peptide sequence. Lys(Dap)-precursors allow high-yield 99mTc-labeling with [99mTc(OH2) 3(CO)3]+, forming small and hydrophilic complexes, which in turn leads to peptide radiopharmaceuticals with excellent in vivo characteristics.
