Sui Qiang, Borchardt Dan, Rabenstein Dallas L
Department of Chemistry, University of California, Riverside, California 92521, USA.
J Am Chem Soc. 2007 Oct 3;129(39):12042-8. doi: 10.1021/ja0740925. Epub 2007 Sep 7.
The biological activities of N-substituted glycine oligomers (peptoids) have been the subject of extensive research. As compared to peptides, both the cis and trans conformations of the backbone amide bonds of peptoids can be significantly populated. Thus, peptoids are mixtures of configurational isomers, with the number of isomers increasing by a factor of 2 with each additional monomer residue. Here we report the results of a study of the kinetics and equilibria of cis/trans isomerization of the amide bonds of N-acetylated peptoid monomers, dipeptoids, and tripeptoids by NMR spectroscopy. Resonance intensities indicate the cis conformation of the backbone amide bonds of the peptoids studied is more populated than is generally the case for the analogous secondary amide bond to proline residues in acyclic peptides. Rate constants were measured by inversion-magnetization transfer techniques over a range of temperatures, and activation parameters were derived from the temperature dependence of the rate constants. The rate of cis/trans isomerization by rotation around the amide bonds in the peptoids studied is generally slower than that around amide bonds to proline residues and takes place on the NMR inversion-magnetization transfer time scale only by rotation around the amide bond to the C-terminal peptoid residue.
N-取代甘氨酸低聚物（类肽）的生物活性一直是广泛研究的主题。与肽相比，类肽主链酰胺键的顺式和反式构象都可能大量存在。因此，类肽是构型异构体的混合物，每增加一个单体残基，异构体的数量就会增加一倍。在这里，我们报告了一项通过核磁共振光谱研究N-乙酰化类肽单体、二肽类和三肽类酰胺键顺/反异构化动力学和平衡的研究结果。共振强度表明，所研究类肽主链酰胺键的顺式构象比无环肽中与脯氨酸残基类似的仲酰胺键的一般情况更为普遍。通过反转磁化转移技术在一系列温度下测量速率常数，并从速率常数的温度依赖性推导出活化参数。所研究类肽中通过围绕酰胺键旋转进行的顺/反异构化速率通常比围绕与脯氨酸残基相连的酰胺键的异构化速率慢，并且仅通过围绕与C末端类肽残基相连的酰胺键旋转在核磁共振反转磁化转移时间尺度上发生。
