FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2083299402> ?p ?o ?g. }

• W2083299402 endingPage "230" @default.
• W2083299402 startingPage "212" @default.
• W2083299402 abstract "High viscosity of monoclonal antibody formulations at concentrations ≥100 mg/mL can impede their development as products suitable for subcutaneous delivery. The effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of MAB 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. The mutations were designed to reduce viscosity by disrupting either an aggregation prone region (APR), which also participates in 2 hydrophobic surface patches, or a negatively charged surface patch in the variable region. The disruption of an APR that lies at the interface of light and heavy chain variable domains, VH and VL, via L45K mutation destabilized MAB 1 and abolished antigen binding. However, mutation at the preceding residue (V44K), which also lies in the same APR, increased apparent solubility and reduced viscosity of MAB 1 without sacrificing antigen binding or thermal stability. Neutralizing the negatively charged surface patch (E59Y) also increased apparent solubility and reduced viscosity of MAB 1, but charge reversal at the same position (E59K/R) caused destabilization, decreased solubility and led to difficulties in sample manipulation that precluded their viscosity measurements at high concentrations. Both V44K and E59Y mutations showed similar increase in apparent solubility. However, the viscosity profile of E59Y was considerably better than that of the V44K, providing evidence that inter-molecular interactions in MAB 1 are electrostatically driven. In conclusion, neutralizing negatively charged surface patches may be more beneficial toward reducing viscosity of highly concentrated antibody solutions than charge reversal or aggregation prone motif disruption." @default.
• W2083299402 created "2016-06-24" @default.
• W2083299402 creator A5002020968 @default.
• W2083299402 creator A5007581467 @default.
• W2083299402 creator A5016983725 @default.
• W2083299402 creator A5017299759 @default.
• W2083299402 creator A5021637441 @default.
• W2083299402 creator A5027475930 @default.
• W2083299402 creator A5042257341 @default.
• W2083299402 creator A5048591673 @default.
• W2083299402 creator A5078146837 @default.
• W2083299402 creator A5085265417 @default.
• W2083299402 date "2015-01-02" @default.
• W2083299402 modified "2023-10-13" @default.
• W2083299402 title "Rational design of viscosity reducing mutants of a monoclonal antibody: Hydrophobic <i>versus</i> electrostatic inter-molecular interactions" @default.
• W2083299402 cites W1972085130 @default.
• W2083299402 cites W1979816062 @default.
• W2083299402 cites W1986431312 @default.
• W2083299402 cites W2005517133 @default.
• W2083299402 cites W2005697596 @default.
• W2083299402 cites W2006141434 @default.
• W2083299402 cites W2007450029 @default.
• W2083299402 cites W2007680384 @default.
• W2083299402 cites W2016076806 @default.
• W2083299402 cites W2021120724 @default.
• W2083299402 cites W2022195665 @default.
• W2083299402 cites W2027839322 @default.
• W2083299402 cites W2029314929 @default.
• W2083299402 cites W2030332033 @default.
• W2083299402 cites W2035890314 @default.
• W2083299402 cites W2036879738 @default.
• W2083299402 cites W2038373191 @default.
• W2083299402 cites W2041528923 @default.
• W2083299402 cites W2041967629 @default.
• W2083299402 cites W2052157693 @default.
• W2083299402 cites W2061792893 @default.
• W2083299402 cites W2062476158 @default.
• W2083299402 cites W2065072784 @default.
• W2083299402 cites W2068530958 @default.
• W2083299402 cites W2073259523 @default.
• W2083299402 cites W2076100371 @default.
• W2083299402 cites W2081787960 @default.
• W2083299402 cites W2086820922 @default.
• W2083299402 cites W2088504288 @default.
• W2083299402 cites W2094328518 @default.
• W2083299402 cites W2095256587 @default.
• W2083299402 cites W2100447023 @default.
• W2083299402 cites W2106243980 @default.
• W2083299402 cites W2132262459 @default.
• W2083299402 cites W2133179696 @default.
• W2083299402 cites W2134439639 @default.
• W2083299402 cites W2137463204 @default.
• W2083299402 cites W2140202728 @default.
• W2083299402 cites W2142760719 @default.
• W2083299402 cites W2146981871 @default.
• W2083299402 cites W2150981663 @default.
• W2083299402 cites W2151727299 @default.
• W2083299402 cites W2159791318 @default.
• W2083299402 cites W2166183482 @default.
• W2083299402 cites W2168193821 @default.
• W2083299402 cites W2319569078 @default.
• W2083299402 cites W2329814377 @default.
• W2083299402 cites W2333638978 @default.
• W2083299402 doi "https://doi.org/10.4161/19420862.2014.985504" @default.
• W2083299402 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4622976" @default.
• W2083299402 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25559441" @default.
• W2083299402 hasPublicationYear "2015" @default.
• W2083299402 type Work @default.
• W2083299402 sameAs 2083299402 @default.
• W2083299402 citedByCount "81" @default.
• W2083299402 countsByYear W20832994022015 @default.
• W2083299402 countsByYear W20832994022016 @default.
• W2083299402 countsByYear W20832994022017 @default.
• W2083299402 countsByYear W20832994022018 @default.
• W2083299402 countsByYear W20832994022019 @default.
• W2083299402 countsByYear W20832994022020 @default.
• W2083299402 countsByYear W20832994022021 @default.
• W2083299402 countsByYear W20832994022022 @default.
• W2083299402 countsByYear W20832994022023 @default.
• W2083299402 crossrefType "journal-article" @default.
• W2083299402 hasAuthorship W2083299402A5002020968 @default.
• W2083299402 hasAuthorship W2083299402A5007581467 @default.
• W2083299402 hasAuthorship W2083299402A5016983725 @default.
• W2083299402 hasAuthorship W2083299402A5017299759 @default.
• W2083299402 hasAuthorship W2083299402A5021637441 @default.
• W2083299402 hasAuthorship W2083299402A5027475930 @default.
• W2083299402 hasAuthorship W2083299402A5042257341 @default.
• W2083299402 hasAuthorship W2083299402A5048591673 @default.
• W2083299402 hasAuthorship W2083299402A5078146837 @default.
• W2083299402 hasAuthorship W2083299402A5085265417 @default.
• W2083299402 hasBestOaLocation W20832994021 @default.
• W2083299402 hasConcept C104317684 @default.
• W2083299402 hasConcept C117626034 @default.
• W2083299402 hasConcept C119599485 @default.
• W2083299402 hasConcept C121332964 @default.
• W2083299402 hasConcept C12554922 @default.
• W2083299402 hasConcept C127172972 @default.
• W2083299402 hasConcept C127413603 @default.

• next