Suchý Mojmír, Li Alex X, Bartha Robert, Hudson Robert H E
Department of Chemistry, The University of Western Ontario, Chemistry Building, Room 209, London, Ont., Canada N6A 5B7.
Bioorg Med Chem. 2008 Jun 1;16(11):6156-66. doi: 10.1016/j.bmc.2008.04.038. Epub 2008 Apr 24.
Chelated lanthanide ions, especially gadolinium, have found wide use as contrast agents in magnetic resonance imaging. A new paradigm for generating contrast, termed PARACEST, was recently described that requires the slow exchange of water or other exchangeable protons present in the ligand framework. In previous work, we have described a synthetic method for the preparation of dipeptide conjugates of DOTAM for use as PARACEST agents. Two compounds possessed interesting magnetic properties: the Eu(3+) complex of DOTAM-Gly-Phe-OH and the Tm(3+) complex of DOTAM-Gly-Lys-OH. To understand the relationship between the structure of these complexes and their magnetic properties, we have expanded our synthetic methodology and prepared several new complexes. Ligands have been prepared in which the terminal phenylalanine moieties have been replaced with tryptophan or tyrosine, the distance to the amino acid residue possessing an alpha-substituent has been changed, or phenylalanine and lysine have been combined in the peptide sequence. The preparation of lanthanide(III) complexes of these ligands has been achieved and their PARACEST properties have been determined.
螯合镧系离子，尤其是钆，已被广泛用作磁共振成像中的造影剂。最近描述了一种产生造影的新范例，称为PARACEST，它需要配体框架中存在的水或其他可交换质子进行缓慢交换。在先前的工作中，我们描述了一种合成方法，用于制备用作PARACEST试剂的DOTAM二肽缀合物。两种化合物具有有趣的磁性：DOTAM-Gly-Phe-OH的Eu(3+)配合物和DOTAM-Gly-Lys-OH的Tm(3+)配合物。为了理解这些配合物的结构与其磁性之间的关系，我们扩展了合成方法并制备了几种新的配合物。已制备了配体，其中末端苯丙氨酸部分已被色氨酸或酪氨酸取代，与具有α-取代基的氨基酸残基的距离已改变，或者苯丙氨酸和赖氨酸已在肽序列中结合。已实现了这些配体的镧系(III)配合物的制备，并确定了它们的PARACEST性质。
