Zelenka, K; Borsig, L; Alberto, R (2011). Metal complex mediated conjugation of peptides to nucleus targeting acridine orange: a modular concept for dual-modality imaging agents. Bioconjugate Chemistry, 22(5):958-967.
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To target the nucleus of specific cells, trifunctional radiopharmaceuticals are required. We have synthesized acridine orange derivatives which comprise an imidazole-2-carbaldehyde function for coordination to the Re(CO)(3)](+) or (99)mTc(CO)(3)](+) core. Upon coordination, this aldehyde is activated and rapidly forms imines with amines from biological molecules. This metal-mediated imine formation allows for the conjugation of a nuclear targeting portion with a specific cell receptor binding function directly on the metal. With this concept, we have conjugated the acridine orange part to a bombesin peptide directly on the (99m)Tc core and in one step. In addition, a linker containing an integrated disulfide has been coupled to bombesin. LC/MS study showed that the disulfide was reductively cleaved with a 60 min half-life time. This concept enables the combination of a nucleus targeting agent with a specific cell receptor molecule directly on the metal without the need of separate conjugation prior to labeling, thus, a modular approach. High uptake of the BBN conjugate into PC-3 cells was detected by fluorescence microscopy, whereas uptake into B16BL6 cells was negligible.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Department of Chemistry|
|Deposited On:||12 Mar 2012 16:28|
|Last Modified:||27 Nov 2013 23:14|
|Publisher:||American Chemical Society|
|Other Identification Number:||ISI:000290691600014|
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