Non-specificity as the sticky problem in therapeutic antibody development.
Nat Rev Chem
; 6(12): 844-861, 2022 12.
Article
en En
| MEDLINE
| ID: mdl-37117703
ABSTRACT
Antibodies are highly potent therapeutic scaffolds with more than a hundred different products approved on the market. Successful development of antibody-based drugs requires a trade-off between high target specificity and target binding affinity. In order to better understand this problem, we here review non-specific interactions and explore their fundamental physicochemical origins. We discuss the role of surface patches - clusters of surface-exposed amino acid residues with similar physicochemical properties - as inducers of non-specific interactions. These patches collectively drive interactions including dipole-dipole, π-stacking and hydrophobic interactions to complementary moieties. We elucidate links between these supramolecular assembly processes and macroscopic development issues, such as decreased physical stability and poor in vivo half-life. Finally, we highlight challenges and opportunities for optimizing protein binding specificity and minimizing non-specificity for future generations of therapeutics.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aminoácidos
/
Anticuerpos
Idioma:
En
Revista:
Nat Rev Chem
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido