The change of corrin-amides to carboxylates leads to altered structures of the B12-responding btuB riboswitch.

By applying four different acid derivatives of vitamin B(12), we demonstrate that the H-bonding pattern and the electrostatic environment provided by each side chain of the corrin ring are crucial for the correct structural rearrangement of the btuB riboswitch of E. coli.

New derivatives of vitamin B12 show preferential targeting of tumors.

Rapidly growing cells show an increased demand for nutrients and vitamins. The objective of our work is to exploit the supply route of vitamin B12 to deliver new derivatives of this vital vitamin to hyperproliferative cells. To date, radiolabeled ((57)Co and (111)In) vitamin B12 derivatives showed labeling of tumor tissue but also undesired high accumulation of radioactivity in normal tissue.

Syntheses and characterization of vitamin B12-Pt(II) conjugates and their adenosylation in an enzymatic assay.

Aiming at the use of vitamin B12 as a drug delivery carrier for cytotoxic agents, we have reacted vitamin B12 with trans-[PtCl(NH3)2(H2O)]+, [PtCl3(NH3)](-) and [PtCl4](2-). These Pt(II) precursors coordinated directly to the Co(III)-bound cyanide, giving the conjugates [(Co)-CN-(trans-PtCl(NH3)2)]+ (5), [(Co)-CN-(trans-PtCl2(NH3))] (6), [(Co)-CN-(cis-PtCl2(NH3))] (7) and [(Co)-CN-(PtCl3)](-) (8) in good yields. Spectroscopic analyses for all compounds and X-ray structure elucidation for 5 and 7 confirmed their authenticity and the presence of the central "Co-CN-Pt" motif.

Picolylamine-methylphosphonic acid esters as tridentate ligands for the labeling of alcohols with the fac-[M(CO)3]+ core (M = 99mTc, Re): synthesis and biodistribution of model compounds and of a 99mTc-labeled cobinamide.

[(Methyl-pyridin-2-ylmethyl-amino)-methyl]-phosphonic acid is a new bifunctional chelator for the fac-[(99m)Tc(CO(3))](+) core which can be linked to biomolecules via formation of phosphonic acid esters. Its synthesis and the coupling to model alcohols and to a bioactive molecule (cobinamide) are described. The rhenium complexes [Re(CO)(3)L] of the esters have been prepared and characterized, one of them by X-ray crystallography.

Cyanide-bridged vitamin B12-cisplatin conjugates.

cis-[PtCl(OH2)(NH3)2]+, the monoactivated form of cisplatin, reacts with the cyano ligand of cobalt in vitamin B12 (cyanocobalamin) to form a Co-C[triple chemical bond]N-Pt conjugate (1). Compound 1 is prepared in good yield directly in aqueous solution. The remaining chloride ligand of Pt(II) is labile.

Mono-, bi-, or tridentate ligands? The labeling of peptides with 99mTc-carbonyls.

The labeling of targeting peptides with (99m)Tc is a useful concept for the diagnosis of various diseases such as cancer. Although in research for at least one decade, only a very few radiopharmaceuticals based on peptides are in clinical use. The difficulty of labeling, and the resulting authenticity of the new vector, is largely responsible for this observation.

Conjugation of a novel histidine derivative to biomolecules and labelling with [99mTc(OH2)3(CO)3]+.

The new histidine derivative 3-[1-[3-(9H-fluoren-9-ylmethoxycarbonylamino)-propyl]-1H-imidazol-4-yl]-2-(3-trimethylsilanyl-ethylcarboxyamino)-propionic acid methyl ester (7) has been prepared via alkylation of the histidine urea derivative (7S)-5,6,7,8-tetrahydro-7-(methoxycarbonyl)-5-oxoimidazo-[1,5-c]-pyrimidine (2) with Fmoc-protected 3-iodopropyl-amine, followed by ring opening with 2-trimethylsilylethanol. After Fmoc cleavage by HNEt2, the histidine amine derivative was coupled to biotin, to the pentapeptide leucine-enkephalin and to Vitamin B12-b-acid by amide formation, employing TBTU as the coupling reagent. In order to make the histidine accessible for labelling, the teoc protecting group was removed by either NBu4F (for the biotin conjugate) or by TFA (for the enkephalin and B12 conjugates).

A new [2 + 1] mixed ligand concept based on [99(m)Tc(OH2)3(CO)3]+: a basic study.

Mixed ligand fac-tricarbonyl complexes of the general formula [M(L1)(L2)(CO)3](M = Re, 99(m)Tc, L1= imidazole, benzyl isocyanide, L2 = 1H-imidazole-4-carboxylic acid, pyridine-2,4-dicarboxylic acid, pyridine-2,5-dicarboxylic acid) have been prepared starting from the precursors [M(OH2)3(CO)3]+. The complexes can be obtained in good yield and purity in a two-step procedure by first attaching the bidentate ligand followed by addition of the monodentate. 99mTc compounds can also be prepared at the tracer level in one-pot procedures with L1 and L2 being concomitantly present.

Preparation of no-carrier-added technetium-99m complexes via metal-assisted cleavage from a solid phase.

A novel method for the preparation of no-carrier-added (nca) complexes [99mTc(CO)3L] (L = diethylenetriamine or picolylamine-N-acetic acid) is described. The ligands were covalently bound to a solid support of organic polymers via formation of a tertiary amine from the chelating unit. This C-N bond to the solid phase is selectively cleaved during the formation of the technetium complexes by intramolecular nucleophilic attack of a remaining hydroxy ligand to the alpha-carbon.