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- Title
Synthesis, characterization, and evaluation of a novel <sup>99m</sup>Tc(CO)<sub>3</sub> pyrazolyl conjugate of a peptide nucleic acid sequence.
- Authors
Xavier, Catarina; Giannini, Clelia; Gano, Lurdes; Maiorana, Stefano; Alberto, Roger; Santos, Isabel
- Abstract
The 16-mer peptide nucleic acid sequence H-A GAT CAT GCC CGG CAT-Lys-NH2 ( 1), which is complementary to the translation start region of the N- myc oncogene messenger RNA, was synthesized and conjugated to a pyrazolyl diamine bifunctional chelator (pz). The novel conjugate pz-A GAT CAT GCC CGG CAT-Lys-NH2 ( 2) was labeled with technetium tricarbonyl, yielding quantitatively the complex fac-[99mTc(CO)3(κ3-pz-A GAT CAT GCC CGG CAT-Lys-NH2)]2+ ( 4). Complex 4 was obtained with high radiochemical purity and high specific activity, revealing high stability in human serum and in cell culture medium. The identity of 4 was confirmed by comparing its reversed-phase high performance liquid chromatography profile with that of the rhenium analog fac-[Re(CO)3(κ3-pz-A GAT CAT GCC CGG CAT-Lys-NH2)]2+ ( 3), prepared by conjugation of fac-[Re(CO)3(3,5-Me2pz(CH2)2N((CH2)3COOH)(CH2)2NH2)]+ to 1, using solid-phase techniques. UV melting experiments of 1 and 3 with the complementary DNA sequence led to the formation of stable duplexes, indicating that the conjugation of 1 to the pyrazolyl chelator and to the metal fragment fac-[M(CO)3]+ did not affect the recognition of the complementary sequence as well as the duplex stability. For a first screening, SH-SY5Y human neuroblastoma cells, which express N- myc, were treated with 4. The results show that 4 internalizes (7% of the activity goes into the cells, after 4 h at 37 °C), presenting also a relatively high cellular retention (only 40% of internalized activity is released from the cells after 5 h).
- Subjects
NUCLEOTIDE sequence; PEPTIDE synthesis; ONCOGENES; MESSENGER RNA; PYRAZOLES; IRON chelates
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2008, Vol 13, Issue 8, p1335
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-008-0419-y