Scientific Reports (Mar 2023)

First pan-specific vNAR against human TGF-β as a potential therapeutic application: in silico modeling assessment

  • Mirna Burciaga-Flores,
  • Ana Laura Márquez-Aguirre,
  • Salvador Dueñas,
  • Jahaziel Gasperin-Bulbarela,
  • Alexei F. Licea-Navarro,
  • Tanya A. Camacho-Villegas

DOI
https://doi.org/10.1038/s41598-023-30623-x
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 13

Abstract

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Abstract Immunotherapies based on antibody fragments have been developed and applied to human diseases, describing novel antibody formats. The vNAR domains have a potential therapeutic use related to their unique properties. This work used a non-immunized Heterodontus francisci shark library to obtain a vNAR with recognition of TGF-β isoforms. The isolated vNAR T1 selected by phage display demonstrated binding of the vNAR T1 to TGF-β isoforms (-β1, -β2, -β3) by direct ELISA assay. These results are supported by using for the first time the Single-Cycle kinetics (SCK) method for Surface plasmon resonance (SPR) analysis for a vNAR. Also, the vNAR T1 shows an equilibrium dissociation constant (K D ) of 9.61 × 10–8 M against rhTGF-β1. Furthermore, the molecular docking analysis revealed that the vNAR T1 interacts with amino acid residues of TGF-β1, which are essential for interaction with type I and II TGF-β receptors. The vNAR T1 is the first pan-specific shark domain reported against the three hTGF-β isoforms and a potential alternative to overcome the challenges related to the modulation of TGF-β levels implicated in several human diseases such as fibrosis, cancer, and COVID-19.