Tryptophan association in water driven by charge-transfer interactions with electron-deficient aromatic haptens. Issue 40 (4th October 2022)

• Record Type: Journal Article
• Authors: Sánchez-Santos, Estela; Garrido-González, José J.; Rodríguez-Sahagún, Ligzajaya F.; Habib, Asmaa; Fuentes de Arriba, Ángel L.; Sanz, Francisca; Martín del Valle, Eva M.; Morán, Joaquín R.; Alcázar, Victoria
• Is Part Of: Organic & biomolecular chemistry. Volume 20:Issue 40(2022)
• Page Start: 7972
• Page End: 7980
• Publication Date: 2022-10-04
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob01650h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Simple electron-deficient aromatic rings bind tryptophan and the tripeptide Trp–Gly–Trp in water by charge-transfer interactions, which might be of interest for the design of drugs targeting protein-protein interactions. Abstract : The ability of a series of electron-deficient aromatic compounds to form charge-transfer complexes with tryptophan in water has been evaluated by X-ray diffraction studies, UV-vis spectra and NMR. As dinitrophenyl (DNP) ligands are well-known to generate antibody-mediated responses and the π–π stacking interactions with tryptophan residues of the antibody Fab fragment have been reported, most of the aromatic receptors studied here are nitro derivatives. Charge-transfer interactions between the rich indole ring of tryptophan and the electron-deficient aromatic receptors have been observed in the solid state, as four crystal structures of the complexes were obtained. The aromatic donor–acceptor interactions in solution were also verified by UV-vis and NMR spectroscopy. The association of the tripeptide Trp–Gly–Trp, a motif found in antigen Ag43, with the electron-deficient aromatic diimide was also studied by UV-vis and NMR spectroscopy. Our results show that these simple electron-deficient molecules could potentially behave as novel haptens and be incorporated in more elaborated drugs targeting protein–protein interactions, due to the synergistic effect of multiple non-covalent interactions.