Bridged bicyclic peptides as potential drug scaffolds: synthesis, structure, protein binding and stability.
Bridged bicyclic peptides as potential drug scaffolds: synthesis, structure, protein binding and stability.
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DOI：
10.1039/c5sc01699a
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发表时间：
2015-10-01
期刊：
影响因子：
8.4
通讯作者：
Reymond JL
中科院分区：
文献类型：
--
作者：
Bartoloni M;Jin X;Marcaida MJ;Banha J;Dibonaventura I;Bongoni S;Bartho K;Gräbner O;Sefkow M;Darbre T;Reymond JL
非对映异构体降冰片多肽是由氨基酸残基的手性决定的球形支架，具有β-Turn和α-螺旋的结构特征。将固相合成法合成的线状短肽进行双环化反应，制得与降冰片等桥联双环烷烃拓扑结构相对应的桥联双环肽。对非对映异构体降冰片多肽进行了1HNMR、X-射线结晶学和圆二色谱的研究，发现它们是由分子内主干氢键稳定的刚性球形支架，支架的几何形状由氨基酸残基的手性决定，并具有β-TURN和α-螺旋的结构特征。捕获化合物质谱仪(CCMS)的蛋白质组谱分析导致发现降冰片多肽27c选择性地与钙调蛋白结合，作为BBP蛋白结合的例子。该BBP和其他BBP对血清中的蛋白降解表现出很高的稳定性。
Diastereomeric norbornapeptides represent globular scaffolds with geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Double cyclization of short linear peptides obtained by solid phase peptide synthesis was used to prepare bridged bicyclic peptides (BBPs) corresponding to the topology of bridged bicyclic alkanes such as norbornane. Diastereomeric norbornapeptides were investigated by 1H-NMR, X-ray crystallography and CD spectroscopy and found to represent rigid globular scaffolds stabilized by intramolecular backbone hydrogen bonds with scaffold geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Proteome profiling by capture compound mass spectrometry (CCMS) led to the discovery of the norbornapeptide 27c binding selectively to calmodulin as an example of a BBP protein binder. This and other BBPs showed high stability towards proteolytic degradation in serum.
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影响因子：
5.7
作者：
Fallon, JL;Halling, DB;Quiocho, FA
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0603873103
发表时间：
2006-12-26
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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