“…Many native nucleases contain metal ions such as Mg(II), Ca(II), Cu(II), and Zn(II), − which enhance catalytic activity by acting as Lewis acid catalysts or activators for either the nucleophilic attack or the leaving group departure. − ,− Early attempts to incorporate a Zn(II) binding moiety in a peptidic scaffold to carry out hydrolytic phosphate cleavage reactions were performed by the Scrimin group. , They installed 2 equiv of an azacrown functionalized amino acid, ( S )-2-amino-3-[1-(1,4,7-triazacyclononane)]propanoic acid (ATANP), into a water-soluble heptapeptide chain that adopts a 3 10 -helix structure. This peptide binds up to 2 equiv of Zn(II) at the azacrown sites, which cooperatively catalyze the cleavage of an RNA model substrate 2-hydroxypropyl- p -nitrophenol phosphate (HPNP) (Scheme , Figure ).…”