Bonnet Dominique, Riché Stéphanie, Loison Stéphanie, Dagher Rania, Frantz Marie-Céline, Boudier Laure, Rahmeh Rita, Mouillac Bernard, Haiech Jacques, Hibert Marcel
Département de Pharmacochimie de la Communication Cellulaire, Université Strasbourg 1, Institut Gilbert Laustriat, CNRS UMR 7175, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, France.
Chemistry. 2008;14(20):6247-54. doi: 10.1002/chem.200800273.
Two novel solid-phase organic tagging (SPOrT) resins were synthesized to facilitate the labeling of peptides and small organic compounds with a fluorescent probe. Both resins were obtained from the commercially available backbone amide linker (BAL) resin. Following the solid-phase synthesis of model compounds, a tripeptide and benzazepine, the fluorescent probe derived from Lissamine Rhodamine B was incorporated through CuI-catalyzed 1,3-dipolar cycloaddition. Final cleavage in acidic media enabled access to both types of molecules in good yield with high purity. The SPOrT resin was successfully applied to the preparation of the first non-peptidic fluorescent compound with a nanomolar affinity for the human vasopressin V2 receptor (V2R) subtype. This molecule will find application in binding assays that use polarization or fluorescence resonance energy-transfer (FRET) techniques. The SPOrT resins are also well suited for other tags and the parallel synthesis of a fluorescently tagged library for protein screening.
合成了两种新型固相有机标记（SPOrT）树脂，以促进用荧光探针标记肽和小有机化合物。两种树脂均由市售的主链酰胺连接体（BAL）树脂制得。在固相合成模型化合物（一种三肽和苯并氮杂䓬）之后，通过碘化亚铜催化的1,3-偶极环加成反应引入了源自丽丝胺罗丹明B的荧光探针。在酸性介质中进行最终裂解，能够以高纯度和良好产率获得这两种类型的分子。SPOrT树脂成功应用于制备对人血管加压素V2受体（V2R）亚型具有纳摩尔亲和力的首个非肽类荧光化合物。该分子将用于采用偏振或荧光共振能量转移（FRET）技术的结合测定。SPOrT树脂也非常适合其他标记以及用于蛋白质筛选的荧光标记文库的平行合成。
