Facile and E-selective intramolecular ring-closing metathesis reactions in 310-helical peptides:: A 3D structural study
Facile and E-selective intramolecular ring-closing metathesis reactions in 310-helical peptides:: A 3D structural study
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DOI：
10.1021/ja071148m
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发表时间：
2007-06-06
影响因子：
15
通讯作者：
O'Leary, Daniel J.
中科院分区：
文献类型：
--
作者：
Boal, Amie K.;Guryanov, Ivan;O'Leary, Daniel J.
闭环复分解反应可用于交联位于3（10）-螺旋肽中i和i + 3位的烯丙基化丝氨酸残基，所述3（10）-螺旋肽含有螺旋氨基酸α-氨基异丁酸（Aib）。发现具有序列Boc-Aib-Aib-Aib-Ser（Al）-Aib-Aib-Ser（Al）-Aib-OMe的八肽在Grubbs第二代催化剂的催化下经历容易且> 20：1的E-选择性闭环复分解（RCM）反应，以产生18元大环。这种交联的形成不会显著干扰肽的天然3（10）-螺旋性，如通过无环二烯、E-烯烃RCM产物及其氢化衍生物的X射线衍射研究所判断的。具有序列Boc-Val-Ser（Al）-Leu-Aib-Ser（Al）-Val-Leu-OMe的七肽系统也经历有效的RCM反应，尽管具有降低的E-选择性。从这些研究中显而易见的是，最小的RCM衍生的大环约束可以容易地掺入3（10）-螺旋肽中。
The ring-closing metathesis reaction can be used to cross-link allylated serine residues situated at the i and i + 3 positions in 3(10)-helical peptides containing the helicogenic amino acid, alpha-aminoisobutyric acid (Aib). An octapeptide with the sequence Boc-Aib-Aib-Aib-Ser(Al)-Aib-Aib-Ser(Al)-Aib-OMe was found to undergo a facile and > 20:1 E-selective ring-closing metathesis (RCM) reaction catalyzed by the Grubbs second-generation catalyst to yield an 18-membered macrocycle. The formation of this cross-link does not significantly disturb the peptide's native 3(10)-helicity, as judged by an X-ray diffraction study of the acyclic diene, the E-olefin RCM product, and its hydrogenated derivative. A heptapeptide system with the sequence Boc-Val-Ser(Al)-Leu-Aib-Ser(Al)-Val-Leu-OMe also underwent an efficient RCM reaction, albeit with diminished E-selectivity. It is apparent from these studies that a minimal, RCM-derived, macrocyclic constraint can be readily incorporated into 3(10)-helical peptides.