|
|||||
|
|
Development of tacrine clusters as positively cooperative systems for the inhibition of acetylcholinesterase |
|
| Authors: | Tereza Cristina Santos Evangelista scar Lpez Sabrina Baptista Ferreira Jos G Fernndez-Bolaos Magne O Sydnes Emil Lindbck |
| Institution: | aDepartment of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway;bDepartment of Organic Chemistry, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;cDepartamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Seville, Spain |
| Abstract: | The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold via linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine clusters displayed a small but significant multivalent inhibition potency in which the binding affinity of each of the tacrine binding units increased up to 3.2 times when they are connected to the central scaffold. |
| Keywords: | Acetylcholinesterase CuAAC multivalent interactions multivalent inhibition potency tacrine |