Valero M L, Camarero J A, Haack T, Mateu M G, Domingo E, Giralt E, Andreu D
Departament de Química Orgànica, Universitat de Barcelona, Barcelona, Spain.
J Mol Recognit. 2000 Jan-Feb;13(1):5-13. doi: 10.1002/(SICI)1099-1352(200001/02)13:1<5::AID-JMR480>3.0.CO;2-L.
Antigenic site A of foot-and-mouth disease virus (serotype C) has been reproduced by means of cyclic versions of peptide A15, YTASARGDLAHLTTT, corresponding to residues 136-150 of envelope protein VP1. A structural basis for the design of the cyclic peptides is provided by crystallographic data from complexes between the Fab fragments of anti-site A monoclonal antibodies and A15, in which the bound peptide is folded into a quasi-cyclic pattern. Head-to-tail cyclizations of A15 do not provide peptides of superior antigenicity. Internal disulfide cyclization, however, leads to analogs which are recognized as one to two orders of magnitude better than linear A15 in both ELISA and biosensor experiments. CD and NMR studies show that the best antigen, CTASARGDLAHLTT-Ahx-C (disulfide), is very insensitive to environment-induced conformational change, suggesting that cyclization helps to stabilize a bioactive-like structure.
口蹄疫病毒（C 型血清型）的抗原位点 A 已通过对应于包膜蛋白 VP1 第 136 - 150 位残基的肽 A15（YTASARGDLAHLTTT）的环状变体得以重现。抗位点 A 单克隆抗体的 Fab 片段与 A15 之间复合物的晶体学数据为环状肽的设计提供了结构基础，其中结合的肽折叠成准环状模式。A15 的头尾环化并未产生具有更高抗原性的肽。然而，内部二硫键环化产生的类似物在 ELISA 和生物传感器实验中被识别的能力比线性 A15 强一到两个数量级。圆二色光谱（CD）和核磁共振（NMR）研究表明，最佳抗原 CTASARGDLAHLTT - Ahx - C（二硫键）对环境诱导的构象变化非常不敏感，这表明环化有助于稳定类似生物活性的结构。
