ENZYME TARGETED IMAGING AGENTS FOR NEUROPSYCHIATRY

低能垒氢键最近被假设为 参与提供酶催化所需的能量的。 这些非常强、低势垒的氢键显示出非常低的场。 质子核磁共振信号(16-20ppm)与低氢分馏 各种因素。烯醇化酶的机制被认为是通过一个 碳负离子中间体，可以通过这样的低屏障来稳定 氢键以中间态存在，而不是基态。它 已被Weiss等人证明。(Jacs，1987) D-TSP(A)的C-2转移质子的分馏因子 竞争性烯醇化酶抑制剂)对催化碱基的影响远低于 团结一心。因为催化部位不存在半胱氨酸残基 为了解释这个发现，正如从x射线晶体结构观察到的那样，它 已经假设这一结果表明存在 低势垒氢键。因此，将使用质子核磁共振来搜索 用于指示这种低势垒氢键的低场信号。 亚甲基磷烯醇式丙酮酸，一种烯醇化酶的缓慢底物，以及 酒石酸半醛磷酸盐，一种死胡同的抑制剂，将是 受雇于研究。在这种情况下使用这种抑制剂 中间体可能以可观的数量存在，希望允许 观察代表低势垒的低场信号的人 氢键。观测到了低场质子核磁共振信号。 胰凝乳酶，由Robillard等人完成。(J.Mol.Biol.，1972)，它有 被认为代表低势垒氢键。

Low-barrier hydrogen bonds have been recently hypothesized to be involved in providing the energy required by enzymes for catalysis. These very strong, low-barrier hydrogen bonds exhibit very low field proton NMR signals (16-20 ppm) and low deuterium fractionation factors. The mechanism of enolase is believed to pass through a carbanion intermediate, which may be stabilized by such a low-barrier hydrogen bond present in the intermediate but not ground state. It has been demonstrated by Weiss, et al. (JACS, 1987) that the fractionation factor for the proton transferred from C-2 of D-TSP (a competitive inhibitor of enolase) to the catalytic base is far below unity. Because no cysteine residues are present in the catalytic site to explain this finding, as observed from x-ray crystal structure, it has been hypothesized that this result suggests the presence of a low-barrier hydrogen bond. Thus, proton NMR will be used to search for a low field signal indicative of such a low-barrier hydrogen bond. Methylene phosphoenolpyruvate, a slow substrate for enolase, and tartronate semialdehyde phosphate, a dead end inhibitor, will be employed for the studies. The use of such inhibitors in which the intermediate may be present in appreciable amounts is hoped to allow one to observe the low field signal representative of a low-barrier hydrogen bond. A low field proton NMR signal has been observed in chymotrypsin by Robillard, et al. (J. Mol. Biol., 1972), which has been postulated to represent a low-barrier hydrogen bond.