CNRS Enzyme and Cell Engineering Laboratory, Université de Technologie de Compiègne, Rue du Docteur Schweitzer, CS 60319, 60203, Compiègne Cedex, France.
Divisions of Engineering in Medicine and Renal Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Angew Chem Int Ed Engl. 2021 Sep 13;60(38):20849-20857. doi: 10.1002/anie.202106507. Epub 2021 Aug 24.
Molecularly imprinted polymers (MIPs) are tailor-made synthetic antibodies possessing specific binding cavities designed for a target molecule. Currently, MIPs for protein targets are synthesized by imprinting a short surface-exposed fragment of the protein, called epitope or antigenic determinant. However, finding the epitope par excellence that will yield a peptide "synthetic antibody" cross-reacting exclusively with the protein from which it is derived, is not easy. We propose a computer-based rational approach to unambiguously identify the "best" epitope candidate. Then, using Saturation Transfer Difference (STD) and WaterLOGSY NMR spectroscopies, we prove the existence of specific binding sites created by the imprinting of this peptide epitope in the MIP nanogel. The optimized MIP nanogel could bind the epitope and cognate protein with a high affinity and selectivity. The study was performed on Hepatitis A Virus Cell Receptor-1 protein, also known as KIM-1 and TIM-1, for its ubiquitous implication in numerous pathologies.
分子印迹聚合物（MIPs）是一种定制的合成抗体，具有针对目标分子的特定结合腔。目前，用于蛋白质靶标的 MIP 是通过印迹蛋白质的短表面暴露片段来合成的，该片段称为表位或抗原决定簇。然而，找到卓越的表位，产生与衍生自其的蛋白质特异性反应的肽“合成抗体”并不容易。我们提出了一种基于计算机的合理方法，可以明确识别“最佳”表位候选物。然后，使用饱和转移差异（STD）和 WaterLOGSY NMR 光谱学，我们证明了在 MIP 纳米凝胶中印迹该肽表位产生的特异性结合位点的存在。优化的 MIP 纳米凝胶可以与表位和同源蛋白高亲和力和选择性地结合。该研究针对肝炎 A 病毒细胞受体-1 蛋白（也称为 KIM-1 和 TIM-1）进行，因为它在许多病理中普遍存在。
