Work

Thermodynamic versus kinetic basis for the high conformational stability of nanobodies for therapeutic applications

Year: 2024

Type: article

Abstract: Nanobodies (NB) are powerful tools for biotechnological and therapeutic applications. They strongly bind to their targets and are very stable. Early studies showed that NB unfolding is reversible and can be analyzed by equilibrium thermodynamics, whereas more recent studies focused on their kinetic stability in very harsh conditions that are far from storage or physiological temperatures (4-37 °C). Here, we show that the thermodynamic view of NB stability holds in a wide range of temperatures (18-100 °C). The thermodynamic stability of three different NBs did not correlate with binding affinity for their target. Alpha-Fold 2 analyses of these NBs showed structural differences in the binding site and hydrogen bond networks. We expect that our approach will be helpful to improve our capacity to enhance structure-function-stability relationships of NB.

Source: FEBS Letters

DOI: 10.1002/1873-3468.15064

Authors: Atanasio Gómez‐Mulas, Mario Cano‐Muñoz, Eduardo Salido Ruiz, Angel Luis Pey

Institutions: Universidad de Granada, Universidad de La Laguna, Hospital Universitario de Canarias, Centre for Biomedical Network Research on Rare Diseases

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $3,790

Funders: Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, Universidad de Granada