Nanofitins and their applications in human health and lung diseases.

Nanofitins, originally known as affitins, are generated from the highly stable DNA-binding protein and chromatin protein (Sac7d) derived from the hyperthermophilic archaeal microorganism Sulfolobus acidocaldarius. 1 Arcus V. OB-fold domains: A snapshot of the evolution of sequence, structure and function. Curr. Opin. Struct. Biol. 2002; 12: 794-801https://doi.org/10.1016/S0959-440X(02)00392-5 Crossref PubMed Scopus (177) Google Scholar The Sac7d protein is well characterized as an oligonucleotide-/oligosaccharide-binding protein based on its high folding capacity due to its five-stranded β-barrel with an α-helix capped structure. Sac7d’s structural motifs recognize a wide range of substrates, such as diverse proteins and metal ions. 1 Arcus V. OB-fold domains: A snapshot of the evolution of sequence, structure and function. Curr. Opin. Struct. Biol. 2002; 12: 794-801https://doi.org/10.1016/S0959-440X(02)00392-5 Crossref PubMed Scopus (177) Google Scholar Approximately two decades ago, Nanofitins, were proposed as artificial binding proteins with favorable biophysical properties and novel ligand specificities to several protein targets in human diseases. At the time, they were considered mimetic artificial antibodies and/or promising scaffold alternative proteins, which have since been modified by molecular engineering, while others have considered their applications based on ribosome display technology. 2 Mouratou B. Béhar G. Paillard-Laurance L. Colinet S. Pecorari F. Ribosome display for the selection of Sac7d scaffolds. in: Douthwaite J.A. Jackson R.H. Ribosome Display and Related Technologies Methods in Molecular Biology. Springer New York, 2012: 315-331https://doi.org/10.1007/978-1-61779-379-0_18 Crossref Scopus (23) Google Scholar The Sac7d protein has also been modified via mutagenesis, increasing its range of binding specificity/capacity as an efficient, widely applicable protein inhibitor in preclinical research that can overcome the inherent deficiencies of antibody fragments or other approaches. 3 Peters W.B. Edmondson S.P. Shriver J.W. Thermodynamics of DNA binding and distortion by the hyperthermophile chromatin protein Sac7d. J. Mol. Biol. 2004; 343: 339-360https://doi.org/10.1016/j.jmb.2004.08.042 Crossref PubMed Scopus (37) Google Scholar