Pharmacophore-Based Strategy for the Development of General and Specific scFv Biosensors for Abused Antibiotics

详细信息    查看全文

• 作者：Mi Young Cha ; Hyang Yeon Lee ; Yeonjin Ko ; Hyunbo Shim ; Seung Bum Park
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：January 19, 2011
• 年：2011
• 卷：22
• 期：1
• 页码：88-94
• 全文大小：358K
• 年卷期：v.22,no.1(January 19, 2011)
• ISSN：1520-4812

文摘

We developed fluorescent biosensor systems that are either general or selective to fluoroquinolone antibiotics by using a single-chain variable-fragment (scFv) as a recognition element. The selectivity of these biosensors to fluoroquinolone antibiotics was rationally tuned through the structural modification on the pharmacophore of fluoroquinolone antibiotics and the subsequent selection of scFv receptor modules against these antibiotics-based antigens using phage display. The resulting A2 and F9 scFv鈥檚 bound to their representative antigen with a moderate affinty (K_D in micromolar range as determined by surface plasmon resonance). A2 is a specific binder for enrofloxacin and did not cross-react with other fluoroquinolone antibiotics including structurally similar ciprofloxacin, while F9 is a general fluoroquinolone binder that likely bound to the antigen at the common pyridone鈭抍arboxylic acid pharmacophore. These scFv-based receptors were successfully applied to the development of one-step fluorescent biosensor which can detect fluoroquinolone antibiotics at concentrations below the level suggested in animal drug application guidelines. The strategy described in this report can be applied to developing convenient field biosensors that can qualitatively detect overused/misused antibiotics in the livestock drinking water.