Satterthwait A C, Arrhenius T, Hagopian R A, Zavala F, Nussenzweig V, Lerner R A
Research Institute of Scripps Clinic, La Jolla, California 92037.
Philos Trans R Soc Lond B Biol Sci. 1989 Jun 12;323(1217):565-72. doi: 10.1098/rstb.1989.0036.
A new strategy is advanced for the conformational restriction of peptidyl immunogens. Our approach is to replace putative amide-amide hydrogen bonds with covalent hydrogen-bond mimics. Because on average every other amino acid in a protein engages in this bond, the syntheses of diversely shaped peptides can be contemplated. Synthetic methods for introducing a potential hydrogen-bond mimic into a peptide with alpha-helical potential is reported and the structural consequences are discussed. The replacement of the hydrogen bond with a chemical link will modify as well as shape the peptide. To explore the consequences of these changes, a potential synthetic vaccine for malaria, the repeating tetrapeptide Asn-Pro-Asn-Ala, was conformationally restricted. Antibodies to the shaped malarial peptide showed a strong cross reaction with Plasmodium falciparum sporozoites.
一种用于肽基免疫原构象限制的新策略被提出。我们的方法是用共价氢键模拟物取代假定的酰胺-酰胺氢键。由于蛋白质中平均每隔一个氨基酸就参与这种键合，因此可以设想合成各种形状的肽。报道了将潜在的氢键模拟物引入具有α-螺旋潜力的肽中的合成方法，并讨论了其结构后果。用化学连接取代氢键将修饰并塑造肽。为了探索这些变化的后果，对一种潜在的疟疾合成疫苗——重复四肽天冬酰胺-脯氨酸-天冬酰胺-丙氨酸进行了构象限制。针对这种形状的疟疾肽产生的抗体与恶性疟原虫子孢子表现出强烈的交叉反应。
