title: A new biochromatography model based on DNA origami assembled PPARγ: construction and evaluation.
abstract: As drug targets, receptors have potential to screen drugs. Silica is an attractive support to immobilize receptors; however, the lack of biocompatibility makes it easier for receptors to lose bioactivity, which remains an obstacle to its widespread use. With the advantage of biocompatibility, DNA origami can be used as a biological carrier to improve the biocompatibility of silica and assemble receptors. In this study, a new biochromatography model based on DNA origami was constructed. A large quantity of M13ssDNA was used as a scaffold, leading to significant costs, so M13ssDNA was self-produced from the bacteriophage particles. This approach is demonstrated using the ligand binding domain of gamma isoform peroxisome proliferator-activated receptor (PPARγ-LBD) as a research object. PPARγ-LBD was assembled on DNA origami carrier and then coupled on the surface of silica. The products were packed into the column as stationary phase to construct the biochromatography with the ability to recognize drugs. Affinity and specificity of the biochromatography model were evaluated by HPLC. The final results showed that the biochromatography could recognize rosiglitazone specifically, which further proved that the model could screen chemical compositions interacted with PPARγ. It was the first time to take advantage of DNA origami to assemble PPARγ to construct biochromatography. The new biochromatography model has the advantages of being efficient, convenient, and high-throughput. This method affords a new way to rapidly and conveniently screen active ingredients from complex sample plant extracts and natural product-like libraries.
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China. jie_0822@163.com.|Collaborative Innovation Center of New Drug Research and Safety Evaluation, No. 100, KeXue DaDao, Zhengzhou, Henan, 450001, China. jie_0822@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China.
authors.forename: Lingchang
authors.initials: L
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Luo
authors.affiliation: School of Pharmacy, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, Henan, 450001, China. zhaoyx@zzu.edu.cn.|Collaborative Innovation Center of New Drug Research and Safety Evaluation, No. 100, KeXue DaDao, Zhengzhou, Henan, 450001, China. zhaoyx@zzu.edu.cn.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D017104:Bacteriophage M13 / Q000737:chemistry*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004277:DNA, Single-Stranded / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000302:isolation & purification*; D055767:Immobilized Proteins / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry; D047495:PPAR gamma / Q000737:chemistry*; D000077154:Rosiglitazone; D012822:Silicon Dioxide / Q000737:chemistry*; D045162:Thiazolidinediones / Q000302:isolation & purification*
chemical_list: D004277:DNA, Single-Stranded; D007004:Hypoglycemic Agents; D055767:Immobilized Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D012822:Silicon Dioxide
keywords: Biochromatography model; DNA origami; HPLC; PPARγ