G-quadruplex recognition by DARPIns through epitope/paratope analogy.

Fiche publication

Date publication

juillet 2022

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GRANDEMANGE Stéphanie

Tous les auteurs :
Miclot T, Bignon E, Terenzi A, Grandemange S, Barone G, Monari A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35791808

Résumé

We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4s specific sensors. To this end we carried out all-atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human-telomeric (h-telo), Bcl-2, and c-Myc, with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c-Myc, we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three-dimensional arrangement of the molecular fragments involved: the α-helix/loops domain of DARPin and the G4 backbone. Our results reveal that DARPins tertiary structure presents a charged hollow region in which G4 can be hosted, thus the more complementary the structural shapes, the more stable the interaction.