Harnessing natures ability to control metal ion coordination geometry using de novo designed peptides.
Advances in protein chemistry and molecular and structural biology have empowered modern chemists to build complex biological architectures using a "first principles" approach, which is known as de novo protein design. In this Perspective we demonstrate how simple three-stranded alpha-helical constructs can be prepared by the sole consideration of the primary amino acid sequence of a peptide. With these well defined systems, we then demonstrate that metal binding cavities can be carved out of the hydrophobic cores of these aggregates in order to bind metal ions such as cadmium with well defined coordination geometries. Examples will be given of homoleptic CdS(3) complexes, CdS(3)O sites and proteins which contain equilibrium mixtures of these two species. We will provide a description of a strategy that allows us to build heterochromic peptides (small proteins that complex two metals in nearly identical environments but which result in different physical properties and allow for metal site selectivity). We conclude with a new class of designed peptides, diastereopeptides, which can exploit changes in amino acid chirality to control metal ion coordination number and lead to an alternative path towards heterochromic systems. The constructs described herein represent the initial steps of preparing protein structures that may simultaneous contain structural and catalytic metal binding centers. These studies inform the community on a developing field, which promises new opportunities for the study of bioinorganic chemistry.
Peacock
Anna F A
AF
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Iranzo
Olga
O
Pecoraro
Vincent L
VL
D000595:Amino Acid Sequence; D002104:Cadmium / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary
D007477:Ions; D009942:Organometallic Compounds; D010455:Peptides; D002104:Cadmium