Universal screening platform using three-dimensional small molecule microarray based on surface plasmon resonance imaging

doi:10.1039/c5ra15637h

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	Universal screening platform using three-dimensional small molecule microarray based on surface plasmon resonance imaging
	Singh, Vikramjeet 1,2,3; Nand, Amita 2,3; Sarita 4
刊名	RSC ADVANCES
	2015
卷号	5 期号:106 页码:87259-87265
ISSN号	2046-2069
DOI	10.1039/c5ra15637h
文献子类	Article
英文摘要	Although much progress has been made in the field of small molecule microarrays in the past decades, its potential has been limited by a lack of efficient methodology. Herein we report a potent methodology for drug screening on a three-dimensional (3D) surface using a carbene based photo-cross-linking reaction. The simultaneous display of a large number of small molecules on a single polymer chain in various orientations allows for the retention of their activity. The presented method was tested using high throughput surface plasmon resonance (SPRi) with the immunosuppressive drugs rapamycin and FK506. We showed that rapamycin and FK506 immobilized on the 3D surface, not the conventional 2D surface, bound to the FKBP with high affinity. Using FKBP-binding ligands and FKBP mutants with altered mutual binding affinities, we observed a strong correlation between the relative binding affinities determined by SPRi and those previously reported. In addition, other important parameters including blocking, washing, robustness and surface reproducibility were also validated. Some well known kinase inhibitors of p38a, JNK and EKR2 proteins were also used to extend the applications of the method. All together, these results suggested that the newly developed 3D small molecule microarray in conjunction with SPRi can be a powerful platform for high throughput drug screening.
WOS关键词	ACTIVATED PROTEIN-KINASE ; INHIBITORS ; DISCOVERY ; DENSITY ; DESIGN ; PROBES ; SITE
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000363233500050
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276698]
专题	药物制剂研究中心
通讯作者	Singh, Vikramjeet
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China; 2.Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China; 3.Univ Chinese Acad, Sci, Beijing 100049, Peoples R China; 4.NIMS Univ Jaipur, Jaipur 303121, Rajasthan, India
推荐引用方式 GB/T 7714	Singh, Vikramjeet,Nand, Amita,Sarita. Universal screening platform using three-dimensional small molecule microarray based on surface plasmon resonance imaging[J]. RSC ADVANCES,2015,5(106):87259-87265.
APA	Singh, Vikramjeet,Nand, Amita,&Sarita.(2015).Universal screening platform using three-dimensional small molecule microarray based on surface plasmon resonance imaging.RSC ADVANCES,5(106),87259-87265.
MLA	Singh, Vikramjeet,et al."Universal screening platform using three-dimensional small molecule microarray based on surface plasmon resonance imaging".RSC ADVANCES 5.106(2015):87259-87265.