Department of Oncology, University of Alberta, Edmonton, Canada.
Bioorg Med Chem. 2012 Apr 1;20(7):2221-6. doi: 10.1016/j.bmc.2012.02.021. Epub 2012 Feb 15.
A series of fluorobenzoylated di- and tripeptides as potential leads for the development of molecular probes for imaging of COX-2 expression was prepared according to standard Fmoc-based solid-phase peptide synthesis. All peptides were assessed for their COX-2 inhibitory potency and selectivity profile in a fluorescence-based COX binding assay. Within the series of 15 peptides tested, cysteine-containing peptides numbered 7, 8, 11 and 12, respectively, were the most potent COX-2 inhibitors possessing IC(50) values ranging from 5 to 85 μM. Fluorobenzoylated tripeptides 7 and 8 displayed some COX-2 selectivity (COX-2 selectivity index 2.1 and 1.6), whereas fluorobenzoylated dipeptides 11 and 12 were shown not to be COX-2 selective. Fluorbenzoylated tripeptide FB-Phe-Cys-Ser-OH was further used in molecular modeling docking studies to determine the binding mode within the active site of the COX-2 enzyme.
根据标准的 Fmoc 固相肽合成法，制备了一系列氟苯甲酰化的二肽和三肽，作为 COX-2 表达成像的分子探针开发的潜在先导化合物。所有肽都在基于荧光的 COX 结合测定中评估了它们对 COX-2 的抑制效力和选择性特征。在所测试的 15 个肽系列中，分别含有半胱氨酸的肽 7、8、11 和 12 是最有效的 COX-2 抑制剂，其 IC50 值范围为 5 至 85 μM。氟苯甲酰化三肽 7 和 8 表现出一定的 COX-2 选择性（COX-2 选择性指数为 2.1 和 1.6），而氟苯甲酰化二肽 11 和 12 则显示不出 COX-2 选择性。氟苯甲酰化三肽 FB-Phe-Cys-Ser-OH 进一步用于分子建模对接研究，以确定在 COX-2 酶的活性部位内的结合模式。
