Forrow Nigel J, Foulds Nicola C, Frew Jane E, Law John T
MediSense (UK) Ltd., Abbott Laboratories, 14/15 Eyston Way, Abingdon, Oxon OX14 1TR, UK.
Bioconjug Chem. 2004 Jan-Feb;15(1):137-44. doi: 10.1021/bc034131b.
A series of 8-(ferrocenylalkyl)theophylline conjugates were synthesized for evaluation in a homogeneous, competitive electrochemical immunoassay for theophylline with amperometric detection of the ferrocene label at +320 mV. The electrical signal was amplified via redox cycling with the glucose oxidase/glucose system. The resulting catalytic current was strongly inhibited upon binding of the conjugates to anti-theophylline antibodies such that a large excess of theophylline was required to achieve complete reversal leading to an assay with poor sensitivity in the clinical range. A study of the nonspecific interaction of the antibodies with various ferrocene derivatives indicated that this was reduced when a charged functional group was present on the metallocene ring. Consequently, a conjugate was synthesized with a quaternary ammonium group which when incorporated into the assay resulted in improved sensitivity.
合成了一系列8 -（二茂铁基烷基）茶碱共轭物，用于在一种均相竞争性电化学免疫测定法中进行评估，该方法用于测定茶碱，并在+320 mV下对二茂铁标记物进行安培检测。通过葡萄糖氧化酶/葡萄糖系统的氧化还原循环放大电信号。当共轭物与抗茶碱抗体结合时，产生的催化电流受到强烈抑制，以至于需要大量过量的茶碱才能实现完全逆转，导致该测定法在临床范围内灵敏度较差。对抗体与各种二茂铁衍生物的非特异性相互作用的研究表明，当金属茂环上存在带电荷的官能团时，这种相互作用会减弱。因此，合成了一种带有季铵基团的共轭物，将其引入测定法中可提高灵敏度。
