Papini A, Rudolph S, Siglmüller G, Musiol H J, Göhring W, Moroder L
Max-Planck-Institute for Biochemistry, Martinsried, Federal Republic of Germany.
Int J Pept Protein Res. 1992 Apr;39(4):348-55. doi: 10.1111/j.1399-3011.1992.tb01594.x.
Introduction of the maleimide function via a spacer into histidine-containing peptides was found to produce ring closure by nucleophilic addition of the Nim-imino function of the histidine side-chain to the activated double bond of the maleimide. As an intramolecular cyclization reaction it proceeds at remarkably higher rates than the bimolecular alkylation of histidine derivatives with N-ethyl-maleimide. Correspondingly, in the case of the histidine-peptides examined only mixtures of the cyclic isomeric compounds were isolated and structurally characterized by 1H-NMR analysis. As expected, prevention of this reaction in histidine-containing maleoyl-peptides can be achieved by Nim-protection of the imidazole group. However, upon removal of this protection, the reaction takes place again, thus remarkably hampering the usefulness of the maleimide/thiol addition principle in conjugate chemistry for peptides. On the other hand this reaction could represent an interesting new approach for the design of cyclic peptidomimetic analogs.
通过间隔基将马来酰亚胺官能团引入含组氨酸的肽中，发现会通过组氨酸侧链的Nim-亚氨基官能团对马来酰亚胺的活化双键进行亲核加成而产生环化。作为分子内环化反应，其进行速率比组氨酸衍生物与N-乙基马来酰亚胺的双分子烷基化反应显著更高。相应地，在所研究的组氨酸肽的情况下，仅分离出环状异构体化合物的混合物，并通过1H-NMR分析对其结构进行了表征。正如预期的那样，通过咪唑基团的Nim保护可以防止含组氨酸的马来酰基肽中的这种反应。然而，去除这种保护后，反应会再次发生，从而显著妨碍了马来酰亚胺/硫醇加成原理在肽共轭化学中的实用性。另一方面，这种反应可能代表了一种设计环状肽模拟类似物的有趣新方法。
