Fuster Cristina, Varese Monica, García Jesús, Giralt Ernest, Sánchez-Navarro Macarena, Teixidó Meritxell
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Department of Inorganic and Organic Chemistry, University of Barcelona, Barcelona, Spain.
J Pept Sci. 2019 May;25(5):e3172. doi: 10.1002/psc.3172.
Venoms have recently emerged as a promising field in drug discovery due to their good selectivity and affinity for a wide range of biological targets. Among their multiple potential applications, venoms are a rich source of blood-brain barrier (BBB) peptide shuttles. We previously described a short nontoxic derivative of apamin, MiniAp-4, which can transport a wide range of cargoes across the BBB. Here, we have studied the conformation of the proline residue of a range of MiniAp-4 analogues by high-field NMR techniques, with the aim to identify whether there is a direct relation between the cis/trans population and a range of features, such as the capacity to transport molecules across a human-based cellular model and stability in various media. The most promising candidate showed improved transport properties for a relevant small fluorophore.
由于毒液对多种生物靶点具有良好的选择性和亲和力，它们最近已成为药物发现领域中一个很有前景的方向。在其多种潜在应用中，毒液是血脑屏障（BBB）肽转运体的丰富来源。我们之前描述了蜂毒明肽的一种短的无毒衍生物MiniAp-4，它可以将多种货物转运穿过血脑屏障。在这里，我们通过高场核磁共振技术研究了一系列MiniAp-4类似物中脯氨酸残基的构象，目的是确定顺式/反式构象比例与一系列特征之间是否存在直接关系，比如跨基于人类的细胞模型转运分子的能力以及在各种介质中的稳定性。最有前景的候选物对一种相关的小荧光团显示出改善的转运特性。
