Micromechanical measurement of AChBP binding for label-free drug discovery.
نویسندگان
چکیده
A potential binding assay based on binding-driven micromechanical motion is described. Acetylcholine binding protein (AChBP) was used to modify a microcantilever. The modified microcantilever was found to bend on application of the naturally occurring agonist (acetylcholine) or the antagonist (nicotine and d-tubocurarine). Control experiments show that microcantilevers modified without AChBP do not respond to acetylcholine, nicotine, and d-tubocurarine. K(d) values obtained for acetylcholine, nicotine, and d-tubocurarine are similar to those obtained from radio-ligand binding assays. These results suggest that the microcantilever system has potential for use in label free, drug screening applications.
منابع مشابه
Micromechanical measurement of membrane receptor binding for label-free drug discovery.
A potential novel binding assay based on binding-driven micromechanical motion is described. A membrane preparation containing 5-HT(3AS) receptors was used to modify a microcantilever. The modified microcantilever was found to bend on application of the naturally occurring agonist (5-hydroxytryptamine, which is also called serotonin) or the antagonist MDL-72222, but not to other similar molecul...
متن کاملFragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis.
Optimization of fragment hits toward high-affinity lead compounds is a crucial aspect of fragment-based drug discovery (FBDD). In the current study, we have successfully optimized a fragment by growing into a ligand-inducible subpocket of the binding site of acetylcholine-binding protein (AChBP). This protein is a soluble homologue of the ligand binding domain (LBD) of Cys-loop receptors. The f...
متن کاملAchbp Fragment Hit
Our constructed ligand efficiency (LE) hot spot surface was used as a guide for structure-based optimization of an AChBP fragment hit. This fragment hit was an analogue of a fragment found in the radioligand binding assay performed on Ls-AChBP, described in Chapter 4. The chemical space around this original fragment was explored by SAR-by-catalogue, thereby increasing its affinity and ligand ef...
متن کاملResidues Responsible for the Selectivity of α-Conotoxins for Ac-AChBP or nAChRs
Nicotinic acetylcholine receptors (nAChRs) are targets for developing new drugs to treat severe pain, nicotine addiction, Alzheimer disease, epilepsy, etc. α-Conotoxins are biologically and chemically diverse. With 12-19 residues and two disulfides, they can be specifically selected for different nAChRs. Acetylcholine-binding proteins from Aplysia californica (Ac-AChBP) are homologous to the li...
متن کاملLabel-free electrochemical biosensors for food and drug application
In food sector, there is a huge demand for rapid, reliable, user & eco-friendly biosensors to analyse the quality and safety of food products. Biosensor based methodology depends upon the recognition of a specific antigens or receptors by corresponding antibodies, aptamers or high-affinity ligands. The first scientifically commercialised sensors were the electrochemical sensors used for the ana...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Analyst
دوره 137 1 شماره
صفحات -
تاریخ انتشار 2012