QSAR of multiple mutated antibodies.
The aim of this study was to develop predictive quantitative structure-activity relationship (QSAR) modeling for antibody-peptide interactions. A small single chain antibody library was designed and manufactured around the murine anti-p24 (HIV-1) monoclonal antibody CB4-1 by use of statistical molecular design (SMD) principles and site directed mutagenesis, and its affinity for a p24 derived antigen was determined by fluorescence polarization. A satisfactory QSAR model (Q(2) = 0.74, R(2) = 0.88) was derived by correlating the affinity data to physicochemical property scales of the amino acids varied in the library. The model explains most of the antibody-antigen interactions of the studied set, and provides insights into the molecular mechanism involved in antigen binding.
Mandrika
Ilona
I
Department of Pharmaceutical Pharmacology, Uppsala University, SE-751 24 Uppasala, Sweden.
Prusis
Peteris
P
Yahorava
Sviatlana
S
Tars
Kaspars
K
Wikberg
Jarl E S
JE
D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008962:Models, Theoretical; D050505:Mutant Proteins / Q000032:analysis*; D009154:Mutation; D019151:Peptide Library; D021281:Quantitative Structure-Activity Relationship; D057127:Single-Chain Antibodies
D000906:Antibodies; D016655:HIV Core Protein p24; D007135:Immunoglobulin Variable Region; D050505:Mutant Proteins; D019151:Peptide Library; C521743:ScFv CB4-1; D057127:Single-Chain Antibodies