L-Penicillamine (Pen) has been investigated as a ligand formetalloprotein design by examining the binding of Co(II) to thesequence NH
2-KL(Pen)EGG·(Pen)
IG(Pen)G
A(Pen)·GGW-CONH
2.For comparison, we have studied Co(II) binding to the analogoussequence with Cys ligands, the ferredoxin maquette ligand
IGAthat was originally designed to bind a [4Fe-4S] cluster. The Co(II)affinity and UV-vis spectroscopic properties of
IGA indicateformation of a pseudotetrahedral tetrathiolate ligated Co(II). Incontrast,
IGA-Pen showed formation of a pseudotetrahedralcomplex with Co(II) bound by three Pen ligands and an exogenousH
2O. EXAFS data on both Co(II) complexes confirms not only theproposed primary coordination spheres but also shows six Co(II)-C
methyl group distances in Co(II)-
IGA-Pen. These resultsdemonstrate that ligand sterics in simple peptides can be designedto provide asymmetric coordination spheres such as thosecommonly observed in natural metalloproteins.