A highly convergent synthesis of myristoyl-carba(dethia)-coenzyme A.
A highly convergent synthesis of myristoyl-carba(dethia)-coenzyme A.
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DOI：
10.1002/ejoc.200901410
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发表时间：
2010-03
影响因子：
2.8
通讯作者：
Retey, Janos
中科院分区：
文献类型：
--
作者：
Tautz, Lutz;Retey, Janos
不同信号蛋白的N-末端甘氨酸残基的共翻译豆蔻酰化是这些分子的膜附着和适当功能所必需的。肉豆蔻酸从肉豆蔻酰辅酶A（myr-CoA）的转移由酶N-肉豆蔻酰转移酶（Nmt）催化。NMT与许多人类疾病有关，包括癌症和癫痫，以及致病机制，如真菌和病毒感染，包括HIV和B型肝炎。合理的设计已经导致开发了有效的竞争性抑制剂，包括几种不可水解的酰基辅酶A底物类似物。然而，遵循原始CoA合成路线的线性合成策略以非常低的总收率产生此类类似物，这通常不足以用于体内研究。在这里，我们提出了一种新的，高度收敛的合成肉豆蔻酰-卡巴（dethia）-辅酶A 1，允许获得这种底物类似物的11倍增加的产量相比，报告的线性合成。此外，在合成的最后步骤中腺苷-2 '，3'-环磷酸的酶促裂解被证明是获得异构纯的3 '-磷酸1的有效方法。
Co-translational myristoylation of the N-terminal glycine residue of diverse signaling proteins is required for membrane attachment and proper function of these molecules. The transfer of myristate from myristoyl-coenzyme A (myr-CoA) is catalyzed by the enzyme N-myristoyltransferase (Nmt). Nmt has been implicated in a number of human diseases, including cancer and epilepsy, as well as pathogenic mechanisms such as fungal and virus infections, including HIV and Hepatitis B. Rational design has led to the development of potent competitive inhibitors, including several non-hydrolysable acyl-CoA substrate analogues. However, linear synthetic strategies, following the route of the original CoA synthesis, generate such analogues in very low over all yields that typically are not sufficient for in vivo studies. Here, we present a new, highly convergent synthesis of myristoyl-carba(dethia)-coenzyme A 1 that allows to obtain this substrate analogue in 11-fold increased yield compared to the reported linear synthesis. In addition, enzymatic cleavage of the adenosine-2',3'-cyclophosphate in the last step of the synthesis proved to be an efficient way to obtain the isomerically pure 3'-phosphate 1.
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DOI：
10.1073/pnas.86.15.5781
发表时间：
1989-08-01
影响因子：
11.1
作者：
GOTTLINGER, HG;SODROSKI, JG;HASELTINE, WA
通讯作者：
HASELTINE, WA
影响因子：
4.1
作者：
KEEP, NH;SMITH, GA;LEADLAY, PF
通讯作者：
LEADLAY, PF
影响因子：
2.7
作者：
Ebiike, H;Masubuchi, M;Shimma, N
通讯作者：
Shimma, N
影响因子：
1.8
作者：
BANNWARTH, W;TRZECIAK, A
通讯作者：
TRZECIAK, A
DOI：
10.1073/pnas.87.2.523
发表时间：
1990-01-01
影响因子：
11.1
作者：
BRYANT, M;RATNER, L
通讯作者：
RATNER, L