Interaction of clinical-stage antibodies with heme predicts their physiochemical and binding qualities.
Commun Biol
; 4(1): 391, 2021 03 23.
Article
em En
| MEDLINE
| ID: mdl-33758329
ABSTRACT
Immunoglobulin repertoires contain a fraction of antibodies that recognize low molecular weight compounds, including some enzymes' cofactors, such as heme. Here, by using a set of 113 samples with variable region sequences matching clinical-stage antibodies, we demonstrated that a considerable number of these antibodies interact with heme. Antibodies that interact with heme possess specific sequence traits of their antigen-binding regions. Moreover they manifest particular physicochemical and functional qualities i.e. increased hydrophobicity, higher propensity of self-binding, higher intrinsic polyreactivity and reduced expression yields. Thus, interaction with heme is a strong predictor of different molecular and functional qualities of antibodies. Notably, these qualities are of high importance for therapeutic antibodies, as their presence was associated with failure of drug candidates to reach clinic. Our study reveled an important facet of information about relationship sequence-function in antibodies. It also offers a convenient tool for detection of liabilities of therapeutic antibodies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Região Variável de Imunoglobulina
/
Heme
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França