38218-77-8Relevant academic research and scientific papers
Structures of the b- and d-acid derivatives of vitamin B12 and their complexes with [M(CO)3]+ (M = 99mTc, Re)
Spingler, Bernhard,Mundwiler, Stefan,Ruiz-Sanchez, Pilar,Van Staveren, Dave R.,Alberto, Roger
, p. 2641 - 2647 (2007)
The acid hydrolysis of natural vitamin B12 yields several products in which the acetamide or propionamide side chains on the corrin framework are converted into the corresponding acids. These acids can be derivatised with further functionalitie
COBALAMINE DERIVATIVES USEFUL FOR DIAGNOSIS AND TREATMENT OF ABNORMAL CELLULAR PROLIFERATION
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Page/Page column 18-19, (2008/06/13)
The invention relates to cobalamin derivatives (a) having no binding affinity or low binding affinity to the transport protein transcobalamin II TCII) and (b) retaining activity as a vitamin B12 substitute, optionally carrying a therapeutic and/or diagnostic agent, such as a radioactive metal. These compounds have a much reduced accumulation rate in blood and benign organs, such as kidney and liver, compared to the accumulation rate in neoplastic tissues, and are more rapidly eliminated from blood. The invention further relates to a method of diagnosis and a method of treatment of a neoplastic disease or an infection by microorganisms in a mammal comprising (a) exposing the mammal to a period of a vitamin B12 - free diet, and (b) subsequently applying a cobalamin derivative of the invention carrying a diagnostic and/or therapeutic agent. By selecting cobalamin derivatives acting as vitamin B12 substitutes, the risk of the formation of resistant off-spring in neoplastic tissue is much reduced.
Conjugation of a novel histidine derivative to biomolecules and labelling with [99mTc(OH2)3(CO)3]+.
van Staveren, Dave R,Mundwiler, Stefan,Hoffmanns, Ulrich,Pak, Jae Kyoung,Spingler, Bernhard,Metzler-Nolte, Nils,Alberto, Roger
, p. 2593 - 2603 (2008/10/09)
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). Reaction of a 10(-4) M solution of the bioconjugates with [99mTc(H2O)3(CO)3]+ at 50 degrees C for 30 min led to the formation of one single new peak in the HPLC radiochromatogram in each case, confirming quantitative labelling of the respective biomolecules. To assess the nature of the labelled compounds, the rhenium analogues with Re(CO)3 were also synthesised and similar retention times confirmed the identity with the 99mTc labelled conjugates.
