1400993-30-7Relevant academic research and scientific papers
Cyclopentadienyl-based amino acids (Cp-aa) as phenylalanine analogues for tumor targeting: Syntheses and biological properties of [(Cp-aa)M(CO) 3](M = Mn, Re, 99mTc)
Sulieman, Samer,Can, Daniel,Mertens, John,N'Dongo, Harmel W. Peindy,Liu, Yu,Schmutz, Paul,Bauwens, Matthias,Spingler, Bernhard,Alberto, Roger
, p. 6880 - 6886 (2012)
Due to an enhanced demand for amino acids, the l-type amino acid transporter 1 (LAT1) is overexpressed in many tumor cell lines. LAT1 represents therefore an attractive target for cancer therapy and diagnosis. On the basis of our reported aqueous synthesis of [(Cp-R)99mTc(CO)3]-type complexes,(1-5) we describe the preparation of unnatural amino acid analogues [(Cp-CH2CH(NH2)COOH)Mn(CO)3] and [(Cp-CH(NH2)COOH)M(CO)3] (M = Mn, Re, 99mTc). Starting from fully protected HC5H5-aa (aa = amino acid), [(Cp-aa)99mTc(CO)3] complexes are accessible in quantitative yields and in a one-step synthesis from [99mTcO 4]-. The rhenium and manganese analogues were prepared and structurally characterized to confirm the authenticity of the 99mTc complex. The inhibition constant of natural phenylalanine (phe) for LAT1 is in the range 70 ± 10 μM. The Ki value of [(Cp-CH(NH 2)COOH)Mn(CO)3] (1a) is 53 ± 11 μM, whereas Ki for the true phe analogue [(Cp-CH 2CH(NH2)COOH)Mn(CO)3] (2) was surprisingly high at 277 ± 37 μM. Complex 1a caused efflux when exposed to cells, underlining its active transport by LAT1 into the cell. 99mTc analogues of small biological lead structures such as amino acids are generally not recognized anymore by their targets, in particular by trans-membrane transporters. The bioorganometallic analogues presented here are, however, actively transported and corroborate the importance of organometallic complexes as mimics of organic lead structures in life sciences.
