An enzymatic route to selenazolines.
An enzymatic route to selenazolines.
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DOI：
10.1002/cbic.201300037
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发表时间：
2013-03-18
期刊：
影响因子：
3.2
通讯作者：
Naismith, James H.
中科院分区：
文献类型：
--
作者：
Koehnke, Jesko;Morawitz, Falk;Bent, Andrew F.;Houssen, Wael E.;Shirran, Sally L.;Fuszard, Matthew A.;Smellie, Iain A.;Botting, Catherine H.;Smith, Margaret C. M.;Jaspars, Marcel;Naismith, James H.
硒杂环化合物（如硒偶氮呋喃）在药物化学中有许多潜在的应用；虽然它们与硫和氧等构，但它们具有不同的化学性质。作为探索生物特性的途径，这种替代是化学家武器库中有价值的补充。硒代唑啉和硒代唑的化学合成涉及使用化学计量量的有毒含硒前体。然而，我们通过给大肠杆菌喂硒半胱氨酸稀释溶液，将硒半胱氨酸纳入底物核糖体肽。我们证明了patellamide的脱水杂环酶和与之密切相关的trunkamide生物合成途径处理含硒半胱氨酸的底物生成硒化氮唑啉，从而建立了酶促合成硒化氮唑啉的途径。这些基团也可以并入大环肽中。尽管这一点尚不清楚，但自然本身可能利用相同的酶来产生天然产物的硒变体。1,3 -硒化唑是药物化学中令人感兴趣的结构基序，因为它们是相应的噻唑的类似物；可以说，最著名的例子是合成化合物硒偶氮呋喃[2](1)和氨selamine[3]（2；方案1）。Zhang等人[4]最近报道了含硒唑环肽（如3）的化学合成及其在p -糖蛋白x射线衍射研究中的应用。近年来，1,3 -硒化唑类药物[1a]也受到了关注，例如，Withers等[5a]报道了一种glcnac衍生的1,3 -硒化唑的合成，该药物被评价为潜在的O-GlcNAcase抑制剂。大多数1,3 -硒化唑的合成路线都是基于Hantzsch合成[1a， 5c, 6]，尽管其他方法也被研究过蓝藻肽是一类由核糖体衍生的含有6 - 20个氨基酸的环状肽，它们由一个较大的前体肽产生，含有广泛的化学修饰，包括杂环、d -立体中心和二硫键。它们是一种有效的生物支架，可以穿过细胞膜，并能抵抗酶的降解Patellamides是cyanobactin家族的成员，由Prochloron didemni产生，Prochloron didemni是在太平洋珊瑚礁中发现的海鞘Lissoclinum patella的专性共生体生物合成途径包括atp依赖的杂环酶PatD、蛋白酶PatA和氧化酶/大环化酶PatG，它们将核糖体前体肽PatE转化为最终的大环（方案2）。髌骨酰胺和变体可以
Selenium heterocycles (eg, selenazofurin) have a number of potential applications in medicinal chemistry; although isosteric with sulfur and oxygen, they have different chemical properties. As a route to exploring biological properties, this substitution is a valuable addition to the chemist’s arsenal. The chemical synthesis of selenazolines and selenazoles involves the use of stoichiometric quantities of toxic selenium-containing precursors. However, we have incorporated selenocysteine into a substrate ribosomal peptide by feeding dilute solutions of selenocysteine to E. coli. We demonstrate that the dehydrating heterocyclases from the patellamide and the closely related trunkamide biosynthetic pathways process selenocysteine-containing substrate to yield selenazoline, thus establishing an enzymatic route to selenazolines. Such groups can also be incorporated into macrocyclic peptides. Although this remains unknown, it is possible that nature itself could utilise the same enzymes to produce selenium variants of natural products. 1, 3-Selenazoles are intriguing structural motifs in medicinal chemistry [1] as they serve as analogues of the corresponding thiazoles; arguably the best-known examples are the synthetic compounds selenazofurin [2](1) and amselamine [3](2; Scheme 1). Zhang et al.[4] recently reported the chemical synthesis of selenazole-containing cyclic peptides (eg, 3) and their application in X-ray diffraction studies of P-glycoprotein. 1, 3-Selenazolines [1a] have also received attention in recent years,[5] for example, Withers et al.[5a] have reported the synthesis of a GlcNAc-derived 1, 3-selenazole that was evaluated as a potential O-GlcNAcase inhibitor. Most synthetic routes to 1, 3-selenazoles are based on the Hantzsch synthesis,[1a, 5c, 6] although other methods have been investigated.[7] Cyanobactins are a family of ribosomally derived cyclic peptides containing six to 20 amino acids, they are produced from a larger precursor peptide and contain extensive chemical modifications including heterocycles, D-stereocentres and disulfide bonds. They are potent biological scaffolds that can cross cell membranes and are resistant to enzymatic degradation.[8] Patellamides are members of the cyanobactin family that are produced by Prochloron didemni, an obligate symbiont of the sea squirt Lissoclinum patella found in Pacific reefs.[9] The biosynthetic pathway involves the ATP-dependent heterocyclase PatD, protease PatA and oxidase/macrocyclase PatG, which convert the ribosomal precursor peptide PatE into the final macrocycle (Scheme 2). Patellamides and variants can be
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影响因子：
16.8
作者：
Koehnke, Jesko;Bent, Andrew;Houssen, Wael E.;Zollman, David;Morawitz, Falk;Shirran, Sally;Vendome, Jeremie;Nneoyiegbe, Ada F.;Trembleau, Laurent;Botting, Catherine H.;Smith, Margaret C. M.;Jaspars, Marcel;Naismith, James H.
通讯作者：
Naismith, James H.
影响因子：
14.8
作者：
Donia, Mohamed S.;Hathaway, Brian J.;Schmidt, Eric W.
通讯作者：
Schmidt, Eric W.
影响因子：
3.5
作者：
Kim, Eun Ju;Love, Dona C.;Darout, Etzer;Abdo, Mohannad;Rempel, Brian;Withers, Stephen G.;Rablen, Paul R.;Hanover, John A.;Knapp, Spencer
通讯作者：
Knapp, Spencer
影响因子：
2.1
作者：
Thomae, David;Perspicace, Enrico;Seck, Pierre
通讯作者：
Seck, Pierre
影响因子：
14.8
作者：
Dunbar, Kyle L.;Melby, Joel O.;Mitchell, Douglas A.
通讯作者：
Mitchell, Douglas A.