3'-Acetyl-3,5-diiodo-L-thyronine: a novel highly active thyromimetic with low receptor affinity.
3'-Acetyl-3,5-diiodo-L-thyronine: a novel highly active thyromimetic with low receptor affinity.
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3-乙酰基-3,5-二碘-L-甲状腺氨酸：一种新型高活性拟甲状腺素，具有低受体亲和力。
DOI：
10.1016/0006-2952(84)90070-4
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发表时间：
1984
影响因子：
5.8
通讯作者：
A. Underwood
中科院分区：
文献类型：
--
作者：
M. Benson;D. Ellis;J. C. Emmett;P. Leeson;N. Pearce;V. P. Shah;A. Underwood
甲状腺激素的 4'-酚羟基在受体结合中起着重要作用，并且有人提出，该羟基与受体的相互作用涉及通过在转座中向激素的 3'-取代基提供酸性氢而形成氢键。为了检验这一假设，我们合成并测量了 3'-乙酰基-3,5-二碘-L-甲状腺氨酸 (3'-Ac-T2) 的肝受体亲和力和拟甲状腺素活性，该化合物中 3'-乙酰基和 4'-羟基之间存在强分子内氢键，从而阻止了这种受体-苯酚氢键的形成。为了证实这一假设，3'-Ac-T2 对分离的大鼠肝核中的 T3 受体具有低亲和力（3,5,3'-三碘-L-甲状腺氨酸，T3 的 0.5%）。相比之下，拟甲状腺活性（通过其诱导大鼠肝甘油-3-磷酸脱氢酶和增加肝切片qO2的能力来评估）大致等于T3的活性。当发现体内给药后3'-Ac-T2占据肝受体的能力比其体外亲和力预测的大约高100倍时，这种明显的差异得到了解决。目前尚不清楚体内和体外核结合之间存在这种差异的原因。
The 4'-phenolic hydroxyl group of thyroid hormones plays an important role in receptor binding, and it has been suggested that the interaction of this hydroxyl group with the receptor involves hydrogen bonding via donation of the acidic hydrogen in atransdisposition to the 3'-substituent of the hormones. In order to test this hypothesis we have synthesised, and measured the hepatic receptor affinity and thyromimetic activity of 3'-acetyl-3,5-diiodo-l-thyronine (3'-Ac-T2), a compound in which the formation of such a receptor-phenol hydrogen bond is precluded by the presence of a strong intramolecular hydrogen bond between the 3'-acetyl- and 4'-hydroxyl groups. In confirmation of the hypothesis, 3'-Ac-T2has a low affinity (0.5% of that of 3,5,3'-triiodo-l-thyronine,T3) for theT3-receptor in isolated rat hepatic nuclei. By contrast the thyromimetic activity (assessed by its ability to induce rat hepatic glycerol-3-phosphate dehydrogenase and increase theqO2of liver slices) was roughly equal to that of T3. This apparent discrepancy was resolved when it was found that the capacity of 3'-Ac-T2to occupy hepatic receptors afterin vivoadministration, was about 100 times greater than predicted from itsin vitroaffinity. The reason for this difference betweenin vivoandin vitronuclear binding is unknown at the present time.
L-和 D-三碘甲状腺原氨酸 (T3) 在大鼠体内的分布和代谢：肝和心脏细胞核优先积累 L-T3，作为 T3 对映体差异生物效力的可能解释。
影响因子：
4.8
作者：
Schwartz,HL;Trence,D;Oppenheimer,JH;Jiang,NS;Jump,DB
通讯作者：
Jump,DB