Laboratory of Chemistry and Biology of Peptides and Proteins, Department of Organic Chemistry "Ugo Schiff", Via della Lastruccia 13, 50019 Sesto Fiorentino, Firenze, Italy.
J Med Chem. 2010 Jan 14;53(1):432-40. doi: 10.1021/jm9014372.
The synthesis of four biotin derivatives carrying two DOTA moieties for each ligand (BisDOTA set) is reported, for increasing radiation/dose ratio and improving efficiency in the pretargeted avidin-biotin radioimmunotherapy. The biotin-containing scaffold of two BisDOTA was similar to the mono-DOTA derivative previously described. Then the scaffold was elongated by trifunctionalized spacers of different length and conjugated with one of the COOH groups of two DOTA. Two others were prepared starting from a on-resin lysine residue. The lysine alpha-NH2 was bonded to biotin, and then spacers were appended to the epsilon-NH2 and conjugated with two DOTA molecules. One compound contained a p-aminobenzoic acid spacer, which ensured higher head-to-tail distance and increased rigidity of the chain. These last two compounds had a very high ability to bond avidin and were labeled with 90Y at high specific activity. All the compounds were resistant to the action of serum biotinidases.
报道了 4 种双（DOTA）衍生物的合成，每个配体携带 2 个 DOTA 部分（双 DOTA 组），用于提高辐射/剂量比并提高靶向性抗生物素蛋白-生物素放射性免疫治疗的效率。两个双 DOTA 的生物素支架类似于先前描述的单 DOTA 衍生物。然后，支架通过不同长度的三官能化间隔物延长，并与两个 DOTA 的一个 COOH 基团连接。另外两个从树脂上的赖氨酸残基开始制备。赖氨酸的α-NH2 与生物素键合，然后间隔物连接到ε-NH2 并与两个 DOTA 分子连接。一种化合物含有对氨基苯甲酸间隔物，这确保了更高的头对头距离和增加了链的刚性。后两种化合物具有与亲和素结合的非常高的能力，并以高比活度标记 90Y。所有化合物均能抵抗血清生物素酶的作用。
