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Rational design of viscosity reducing mutants of a monoclonal antibody: hydrophobic versus electrostatic inter-molecular interactions.
Nichols, Pilarin; Li, Li; Kumar, Sandeep; Buck, Patrick M; Singh, Satish K; Goswami, Sumit; Balthazor, Bryan; Conley, Tami R; Sek, David; Allen, Martin J.
Afiliação
  • Nichols P; a Biotherapeutics Pharmaceutical Sciences Research and Development; Pfizer Inc. ; Andover , MA USA.
MAbs ; 7(1): 212-30, 2015.
Article em En | MEDLINE | ID: mdl-25559441
Assuntos
Palavras-chave
APR, Aggregation Prone Region; ASA, Accessible Surface Area; ASAFv-HPH, hydrophilic accessible surface area of the Fv portion; ASAFv-HYD, hydrophobic accessible surface area of the Fv portion; CE, Capillary Electrophoresis; CH2; CH3, third constant domain in heavy chain; CHO, Chinese Hamster Ovary; D0, diffusion coefficient at infinite dilution; DFv, dipole moment of Fv; DLS, Dynamic Light Scattering; ELISA, Enzyme-Linked Immunosorbent Assay; Fab, fragment antigen binding; Fc, fragment crystallizable; Fv, fragment variable; HC, heavy chain; IgG, immunoglobulin G; LC, light chain; MAB 1 Control, MAB 1 expressed in CHO cells; MD, molecular dynamics; NTU, Nephelometric Turbidity Unit; PEG, polyethylene glycol; Pagg-VH, aggregation propensity of VH domain; Pagg-VL, aggregation propensity of VL domain; RPM, revolutions per minute; SE-HPLC, Size Exclusion High Performance Liquid Chromatography; Tm, thermal transition temperature; VH, variable domain in the heavy chain; VL, variable domain in the light chain; ZDHH, Debye-Huckel Henry Charge; ZFv, net charge of the Fv; ZFv-app, apparent charge of the Fv; aggregation prone regions; cIEF, capillary Isoelectric Focusing; cP, centipoise; high concentration; kD, protein-protein interaction parameter; mAb, monoclonal antibody; molecular modeling; monoclonal antibodies; negatively charged patches; rational design; second constant domain in the heavy chain; solubility; viscosity; ΔGFv, change in Free energy of Fv; η, solution viscosity; η0, solvent viscosity; ηrel, relative viscosity; ξFv, zeta-potential of the Fv

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mutação Puntual / Substituição de Aminoácidos / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: MAbs Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mutação Puntual / Substituição de Aminoácidos / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: MAbs Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2015 Tipo de documento: Article