English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

An antibody mimetic known as Fab-PEG-Fab (FpF) is a stable bivalent molecule that may have some potential therapeutic advantages over IgG antibodies due to differences in their binding kinetics as determined by surface plasmon resonance. Here we describe the thermodynamic binding properties to vascular endothelial growth factor (VEGF) of the FpF antibody mimetics derived from bevacizumab and ranibizumab. Bevacizumab is an IgG antibody and ranibizumab is an antibody fragment (Fab). Both are used clinically to target VEGF to inhibit angiogenesis. FpF beva displayed comparable binding affinity (KD) and binding thermodynamics (Δ H = -25.7 kcal mole -1 and Δ S = 14 kcal mole -1 ) to bevacizumab (Δ H = -25 kcal mole -1 , Δ S = 13.3 kcal mole -1 ). FpF rani interactions with VEGF were characterised by large favourable enthalpy (Δ H = -42 kcal mole -1 ) and unfavourable entropy (Δ S = 31 kcal mole -1 ) changes compared to ranibizumab (Δ H = -18.5 kcal mole -1 and Δ S = 6.7 kcal mole -1 ), which being a Fab, is mono-valent. A large negative entropy change resulting in binding of bivalent FpF to homodimer VEGF might be due to the conformational change of the flexible regions of the FpF upon ligand binding. Mono-valent Fab ( i.e. ranibizumab or the Fab derived from bevacizumab) displayed a larger degree of freedom (smaller unfavourable entropy) upon binding to homodimer VEGF. Our report describes the first comprehensive enthalpy and entropy compensation analysis for FpF antibody mimetics. While the FpFs displayed similar thermodynamics and binding affinity to the full IgG ( i.e. bevacizumab), their enhanced protein stability, slower dissociation rate and lack of Fc effector functions could make FpF a potential next-generation therapy for local tissue-targeted indications.

Comparative thermodynamic analysis in solution of a next generation antibody mimetic to VEGF