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Enthalpy‐ versus Entropy‐Driven Molecular Recognition in the Era of Biologics
Author(s) -
Varese Monica,
Guardiola Salvador,
García Jesús,
Giralt Ernest
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900270
Subject(s) - molecular recognition , computational biology , epidermal growth factor receptor , chemistry , entropy (arrow of time) , small molecule , mechanism (biology) , antibody , receptor , nanotechnology , molecule , biology , materials science , biochemistry , thermodynamics , physics , immunology , organic chemistry , quantum mechanics
Our laboratory has recently identified two nanobodies (small antibodies produced by camelids)—Nb1 and Nb6—that bind efficiently to epithelial growth factor (EGF) and inhibit its ability to activate its receptor (EGFR). Because of the relevance of the EGF/EGFR axis as a target in oncology, these new nanobodies have promising therapeutic potential. This article, however, is focused on another feature of these nanobodies: their distinct thermodynamic signatures. Nb1 binds to EGF through an entropy‐driven mechanism whereas Nb6 binds to this factor under enthalpic control. We discuss the advantages and disadvantages of each mechanism in the contexts of traditional medical chemistry (small‐molecule drugs) and also of biological drugs. In this latter case, the implications in terms of selectivity are far from being clearly established and further experimental data are required. Their monomeric natures, high stability, and ease of recombinant production make nanobodies ideally suited for thermodynamic studies. Moreover, nanobodies, thanks to their simpler structures in comparison with conventional antibodies, might provide better understanding of the structural basis of the thermodynamic parameters of antigen recognition.