当前位置：
X-MOL 学术
›
Bioconjugate Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Blood-Brain Barrier Penetrating Luminescent Conjugates Based on Cyclometalated Platinum(II) Complexes
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-10-13 , DOI: 10.1021/acs.bioconjchem.0c00542 Anastasia I Solomatina 1 , Aleksandra D Slobodina 2 , Elena V Ryabova 2 , Olga I Bolshakova 2 , Pavel S Chelushkin 1 , Svetlana V Sarantseva 2 , Sergey P Tunik 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-10-13 , DOI: 10.1021/acs.bioconjchem.0c00542 Anastasia I Solomatina 1 , Aleksandra D Slobodina 2 , Elena V Ryabova 2 , Olga I Bolshakova 2 , Pavel S Chelushkin 1 , Svetlana V Sarantseva 2 , Sergey P Tunik 1
Affiliation
|
Herein we report on the synthesis, structural characterization and photophysical properties of cyclometalated Pt(II) complexes [Pt(N^C)(PPh2(C6H4COOH))Cl] (where N^C ligands are 2-phenylpyridine, (2-benzofuran-3-yl)pyridine, and (2-benzo[b]tiophen-3-yl)pyridine) and their conjugates with the histidine-containing RRRRRRRRRRHVLPKVQA peptide. This peptide contains the RHVLPKVQA sequence, which is responsible for antiamyloid activity, and the Arg9 RRRRRRRRR domain, which shows improved translocation through cell membranes. The chemistry underpinning the conjugation is regioselective complexation between Pt(II) complexes and histidine residue in the peptide. The prepared conjugates have been characterized using high-resolution mass spectrometry and NMR spectroscopy. It was shown that the conjugates are easily soluble in aqueous media and display emission band profiles essentially similar to those of the starting complexes but considerably higher luminescence quantum yield and much longer phosphorescence lifetime. MTT assay on HeLa cell culture revealed no cytotoxicity up to 10 μM after 24 h of incubation. Ex vivo and in vivo neuroimaging experiments on both wild and amyloid peptide expressing strains of Drosophila melanogaster revealed that the conjugates penetrate the blood-brain barrier and are evenly distributed throughout the brain independently of the strain used.
中文翻译：
基于环金属化铂（II）配合物的血脑屏障穿透发光共轭物。
本文中，我们报道了环金属化Pt（II）配合物[Pt（N ^ C）（PPh 2（C 6 H 4 COOH））Cl]的合成，结构表征和光物理性质（其中N ^ C配体为2-苯基吡啶， （2-苯并呋喃-3-基）吡啶和（2-苯并[ b[噻吩-3-基）吡啶）及其与含组氨酸的RRRRRRRRRHLVLPKPKVQA肽的缀合物。该肽包含负责抗淀粉样蛋白活性的RHVLPKVQA序列，以及显示出改善的通过细胞膜易位的Arg9RRRRRRRR域。缀合的化学基础是肽中Pt（II）配合物和组氨酸残基之间的区域选择性配合。制备的结合物已经使用高分辨率质谱和NMR光谱进行了表征。结果表明，缀合物易于溶于水性介质，并显示出与起始络合物基本相似的发射带谱，但发光量子产率更高，磷光寿命更长。在HeLa细胞培养物中进行的MTT分析显示，孵育24小时后，直至10μM都没有细胞毒性。野生和淀粉样肽表达菌株的离体和体内神经成像实验果蝇果蝇揭示，结合物穿透血脑屏障并独立于所使用的菌株均匀地分布在整个大脑中。
更新日期：2020-11-18
中文翻译：
基于环金属化铂（II）配合物的血脑屏障穿透发光共轭物。
本文中，我们报道了环金属化Pt（II）配合物[Pt（N ^ C）（PPh 2（C 6 H 4 COOH））Cl]的合成，结构表征和光物理性质（其中N ^ C配体为2-苯基吡啶， （2-苯并呋喃-3-基）吡啶和（2-苯并[ b[噻吩-3-基）吡啶）及其与含组氨酸的RRRRRRRRRHLVLPKPKVQA肽的缀合物。该肽包含负责抗淀粉样蛋白活性的RHVLPKVQA序列，以及显示出改善的通过细胞膜易位的Arg9RRRRRRRR域。缀合的化学基础是肽中Pt（II）配合物和组氨酸残基之间的区域选择性配合。制备的结合物已经使用高分辨率质谱和NMR光谱进行了表征。结果表明，缀合物易于溶于水性介质，并显示出与起始络合物基本相似的发射带谱，但发光量子产率更高，磷光寿命更长。在HeLa细胞培养物中进行的MTT分析显示，孵育24小时后，直至10μM都没有细胞毒性。野生和淀粉样肽表达菌株的离体和体内神经成像实验果蝇果蝇揭示，结合物穿透血脑屏障并独立于所使用的菌株均匀地分布在整个大脑中。
京公网安备 11010802027423号