Identification and localization of the fatty acid modification in ghrelin by electron capture dissociation
Identification and localization of the fatty acid modification in ghrelin by electron capture dissociation
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DOI：
10.1016/s1044-0305(02)00707-9
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发表时间：
2002-12-01
影响因子：
3.2
通讯作者：
Guan, ZQ
中科院分区：
文献类型：
--
作者：
Guan, ZQ
电子捕获解离（ECD）已被证明是一种有效的碎片化技术，用于表征胃饥饿素中脂肪酸修饰的位置和结构，胃饥饿素是一种28个残基的生长激素释放肽，在Ser-3上有一个不寻常的酯连接的正辛烷基（C8:0）修饰。ECD切割23个可能的主胺键中的21个，产物离子（c和z离子）覆盖的氨基酸序列比碰撞激活解离（CAD）获得的氨基酸序列更大。与ECD非过能机制一致，酯连接的辛烷基保留在所有主裂解产物离子上，允许这种不稳定修饰的直接定位。此外，ECD还诱导酯键断裂，导致胃饥饿素分子离子中辛酸的丢失；消除过程是由质子化酯基上的一个电子的捕获开始的，随后是被称为a-裂解的自由基位点引发的反应。通过对酯键裂解产物离子进行精确的傅立叶变换离子回旋共振（FTICR）质量测量，可以直接得到附着脂肪酸的化学组成。
Electron capture dissociation (ECD) has been demonstrated to be an effective fragmentation technique for characterizing the site and structure of the fatty acid modification in ghrelin, a 28-residue growth-hormone-releasing peptide that has an unusual ester-linked n-octanoyl (C8:0) modification at Ser-3. ECD cleaves 21 of 23 possible backbone amine bonds, with the product ions (c and z. ions) covering a greater amino acid sequence than those obtained by collisionally activated dissociation (CAD). Consistent with the ECD nonergodic mechanism, the ester-linked octanoyl group is retained on all backbone cleavage product ions, allowing for direct localization of this labile modification. In addition, ECD also induces the ester bond cleavage to cause the loss of octanoic acid from the ghrelin molecular ion; the elimination process is initiated by the capture of an electron at the protonated ester group, which is followed by the radical-site-initiated reaction known as a-cleavage. The chemical composition of the attached fatty acid can be directly obtained from the accurate Fourier transform ion cyclotron resonance (FTICR) mass measurement of the ester bond cleavage product ions.