Description: The mirror-image phage display library screening methodology is an innovative approach in drug discovery which ultimately led to the identification of metabolically stable peptide molecules as binders of a protein target. In mirror-image phage display, the D-enantiomer form of the protein target, that is the mirror-image conformation of the natural protein, is used as bait in libraries screening experiments leading to the selection of L-peptide binders, which, when inverted in their D-form, for symmetry, are able to bind the native L-protein target. A mirror protein can only be prepared by chemical route, using chemical ligation approaches. We apply mirror-image phage display to the selection of D-peptide binders of Axl receptor, a novel interesting protein target in biomedicine. To this aim we set up the chemical procedure for the total chemical synthesis of the extracellular domains of Axl receptor, such as Ig2 domain, in their mirror form and we use such proteins in library screening experiments.
Total chemical synthesis by native chemical ligation of the all-Dimmunoglobulin-like domain 2 of Axl
De Rosa L,
DiStasi R, D’Andrea L D. Tetrahedron. 2019, 75, 894-905. DOI: