Jesus M Aizpurua, José I Miranda, Aitziber Irastorza, Endika Torres, Maite Eceiza, Maialen Sagartzazu-Aizpurua, Pablo Ferrón, Garazi Aldanondo, Haizpea Lasa-Fernández, Pablo Marco-Moreno, Naroa Dadie, Adolfo López de Munain, Ainara Vallejo-Illarramendi
The hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through molecular "reshaping" of FKBP12 was investigated. To this end, novel 4-arylthioalkyl-1-carboxyalkyl-1,2,3-triazoles were designed and synthesized, and their efficacy was tested in human myotubes. A library of 17 compounds (10a-n) designed to dock the FKBP12/RyR1 hot-spot interface contact residues, was readily prepared from free α-amino acids and arylthioalkynes using CuAAC "click" protocols amenable to one-pot transformations in high overall yields and total configurational integrity...
January 14, 2021: European Journal of Medicinal Chemistry