Note: How Big Is Too Big for Cell Permeability?
Note: How Big Is Too Big for Cell Permeability? Doi: 10.1021/acs.jmedchem.7b00237 Prediction from human proteome to have protein-protein interactions; 100,000 - 1,000,000 (PPI) Challenges for PPI (nonclassical drug targets) Large Featureless (no unique characteristic) Flexible interfaces Mostly, located inside the cells Biologics drug; Lack of cell permeability Low bioavailability on oral administration In chemical side -- it is really important to understand the chemical space of peptides which contain following properties Cell permeable Drug-like molecules This paper mentioned “cyclic peptide” chemical space. What Cameron Pye did; Evaluate the impact of molecular size + lipophilicity on membrane permeability To check membrane permeability; Using artificial membrane permeability assay (PAMPA) MDCK (Madin-Darby canine kidney) cell clone (expresses low levels of P-glycoprotein -- efflux transporter) **This size-dependent permeability is not compatible with the traditional solubility − d...