About 30 % of all amino acids in proteins are found in a helices. [1] When buried in the hydrophobic interiors of proteins, helices are important in stabilizing tertiary structures, promoting protein folding, and molding active sites of enzymes. However, short peptides (< 15 amino acids) corresponding to such helices are usually unstructured outside of their hydrophobic protein environments. [2] Attempts to produce short, stable a helices by using noncovalent side chain constraints (e.g., salt bridges, hydrophobic interactions), [3a,b] covalent side chain linkers (e.g., disulfide, [3c] hydrazone, [3d] aliphatic, [3e] lactam [3f] bridges) have met with some success. However, little is known about the capacity of metal ions to stabilize a helicity in short peptides, [4] even though metals are often bound to the helical regions of metalloproteins. [5] Here we report that at 300 K [Pd(en)] 2þ induces helicity in 5-, 10-, and 15-residue nonhelical peptides corresponding to the Zn 2þ -binding a helix of the active site of thermolysin (Figure 1). Formation of an unusual 22-membered macrocycle in the metallopentapeptides 1±3, by metal coordination to two histidine residues spaced three residues apart (i.e. i, i þ 4), results in helical structures in solution that are analogous to those in the thermolysin crystal structure. [6] Reaction of [Pd( 15 NH 2 CH 2 CH 2 15 NH 2 )(ONO 2 ) 2 ] with one equivalent of each of the following thermolysin fragments [7] Ac-H*ELTH*-NH 2 ( 4), Ac-H*ELTH*-AVTDY-NH 2 (5) and Ac-IDVVA-H*ELTH*-AVTDY-NH 2 (6) (Ac ¼ acetyl) in DMF (or water) exclusively led to the respective metallopeptide products 1±3, which were unambiguously characterized by multinuclear ( 1 H, 15 N, 13 C) and 2D NMR spectroscopy (see Supporting Information). Formation of a [Pd(en)(peptide)] 2þ product 1, with 1:1 en:peptide stoichiometry, from 4 was supported by an unambiguously assigned single set of peptide 1 H NMR resonances (Figure 2 a). The resonances of the imidazole protons H2 and H5 of both histidine residues (H*1 H2, H*5 H2, H*1 H5, H*5 H5) are shifted significantly after palladium addition. The 15 N NMR spectrum of 1 exhibited just two resonances (Figure 2 b), both upfield of the resonance of [Pd( 15 NH 2 CH 2 CH 2 15