title: Competition binding experiments for rapidly ranking lead molecules for their binding affinity to human serum albumin.
abstract: Many lead molecules that have high affinity for a therapeutic target in vitro exhibit a reduced efficacy in vivo. Drug binding to human serum albumin is a major contributor to this reduction in potency, and many drug discovery programs expand significant resources preparing compounds that have decreased albumin binding. As rational and structure-based approaches have already been demonstrated to design compounds that have reduced affinity for albumin, the ability to rapidly and accurately assess protein binding will be valuable in lead optimization. This review will summarize some of the NMR-based efforts towards developing universal, rapid, accurate, and site-specific assays for estimating protein binding.
authors.affiliation: Chemistry Department, Pharmacia, Viale Pasteur 10, Nerviano (MI), 20014, Italy. claudio.dalvit@pharmacia.com
authors.forename: Claudio
authors.initials: C
authors.lastname: Dalvit
authors.forename: Maria
authors.initials: M
authors.lastname: Flocco
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stockman
authors.forename: Marina
authors.initials: M
authors.lastname: Veronesi
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D012709:Serum Albumin; D014364:Tryptophan