Chemoselective Esterification of Natural and Prebiotic 1,2-Amino Alcohol Amphiphiles in Water.
Chemoselective Esterification of Natural and Prebiotic 1,2-Amino Alcohol Amphiphiles in Water.
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天然和益生元1，2-氨基醇两亲物在水中的化学选择性酯化。
DOI：
10.1021/jacs.3c12038
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发表时间：
2023-12-13
影响因子：
15
通讯作者：
Devaraj, Neal K.
中科院分区：
文献类型：
--
作者：
Bhattacharya, Ahanjit;Tanwar, Lalita;Fracassi, Alessandro;Brea, Roberto J.;Salvador-Castell, Marta;Khanal, Satyam;Sinha, Sunil K.;Devaraj, Neal K.
在细胞中，大量的膜脂质是通过极性头部基团与酰化剂如脂肪酰辅酶A的酶促O-酰化形成的。虽然这种含酯的脂质似乎是地球上生命的必需品，但目前尚不清楚类似类型的脂质是否可以在生命起源时没有酶机制的情况下自发形成。在水中两亲物的无酶酯化的例子很少，并且在生理pH下使用生物化学相关的酰化剂在水中也不会发生。在这里，我们报告了意想不到的化学选择性O-酰化的1，2-氨基醇两亲物在水中指导铜（II）和其他几种过渡金属离子。在含有Cu（II）离子的缓冲液中，混合生物1，2-氨基醇两亲物，如鞘氨醇磷酸胆碱与生化相关的酰化剂，即酰基腺苷酸和酰基辅酶A，导致形成的O-酰化产物具有高选择性。所得到的O-酰化鞘脂自组装成囊泡，具有显着不同的生物物理特性比那些形成从他们的N-酰基对应物。我们还表明，铜（II）可以直接的O-酰化的替代1，2-氨基醇，包括prebiotically相关的1，2-氨基醇两亲物，这表明简单的水酯化机制可能已经普遍存在于地球上的酶进化之前。
In cells, a vast number of membrane lipids are formed by the enzymatic O-acylation of polar head groups with acylating agents such as fatty acyl-CoAs. Although such ester-containing lipids appear to be a requirement for life on earth, it is unclear if similar types of lipids could have spontaneously formed in the absence of enzymatic machinery at the origin of life. There are few examples of enzyme-free esterification of amphiphiles in water and none that can occur in water at physiological pH using biochemically relevant acylating agents. Here we report the unexpected chemoselective O-acylation of 1,2-amino alcohol amphiphiles in water directed by Cu(II) and several other transition metal ions. In buffers containing Cu(II) ions, mixing biological 1,2-amino alcohol amphiphiles such as sphingosylphosphorylcholine with biochemically relevant acylating agents, namely, acyl adenylates and acyl-CoAs, leads to the formation of the O-acylation product with high selectivity. The resulting O-acylated sphingolipids self-assemble into vesicles with markedly different biophysical properties than those formed from their N-acyl counterparts. We also demonstrate that Cu(II) can direct the O-acylation of alternative 1,2-amino alcohols, including prebiotically relevant 1,2-amino alcohol amphiphiles, suggesting that simple mechanisms for aqueous esterification may have been prevalent on earth before the evolution of enzymes.
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影响因子：
8.4
作者：
Liu Z;Mariani A;Wu L;Ritson D;Folli A;Murphy D;Sutherland J
通讯作者：
Sutherland J
DOI：
10.1073/pnas.1210029109
发表时间：
2012-09-25
影响因子：
11.1
作者：
Griffith, Elizabeth C.;Vaida, Veronica
通讯作者：
Vaida, Veronica
影响因子：
15
作者：
Cameron, LL;Wang, SC;Kluger, R
通讯作者：
Kluger, R
影响因子：
3.4
作者：
Jimenez-Rojo, Noemi;Garcia-Arribas, Aritz B.;Goni, Felix M.
通讯作者：
Goni, Felix M.
影响因子：
1.9
作者：
Breilyn MS;Zhang W;Yu C;Wasserstein MP
通讯作者：
Wasserstein MP