Hexapeptide and Heptapeptide Rings

Whereas transannular hydrogen bonds, either single 4 - 1 types, a pair of 3 - 1 types, or a combination of a 3 - 1 and a 4 - 1 type, have already been observed in the tetra- and pentapeptide rings, pairs of 4 - 1 types of hydrogen bonds begin to appear in cyclic hexapeptides. However, it will be shown that transannular hydrogen bonds are not necessarily essential to the conforma- 

A new phenomenon is introduced with the cyclic hexapeptides in that the same compound can assume a number of different conformations. For example, each unit cell in the crystal of cyclic hexaglycine contains four different conformers of the molecule (Karle and Karle, 1963). Each conformer has all-trans planar peptide groups, but only one conformer contains intramolecular hydrogen bonds, a pair of parallel 4 1 bonds (Fig. 9). Two of the conformers contain a center of symmetry coincident with centers in the crystal the conformer with the transannular hydrogen bonds also contains a center, although it is not required by the symmetry elements of the crystal and the fourth conformer is asymmetric. The centers of symmetry in the cyclo Gly)e molecules are possible since glycine residues do not contain asymmetric C atoms. 

The rings in cyc/o(Gly-DAla-DAla-Gly-Gly-Gly) (Karle et ai, 1970) and cyc/o(Gly-LAla-Gly-Gly-LAla-LAla) (Hossain and van der Helm, 1978) have a conformation almost identical to that of conformer (a) of cyclo Gly) with two intraannular hydrogen bonds. The methyl groups of the D-alanine and L-alanine residues are located at the corners of the 4 1 hydrogen bonds. 

A number of substances of the ferrichrome family, containing three hydroxamic acid groups coordinated to a central ferric ion, have been isolated, mainly from microbial sources. These compounds contain a cyclic hexapeptide. Crystal structures for ferrichrome A, cyc/o[LSer-LSer-Gly-Tri ((5-N-methylglutaconyl-5-N-hydroxy-Orn)] (Figs. 11 and 12) (Zalkin et al, 1966), the isomorphous alumichrome A (van der Helm et ai, 1980), and more recently ferrichrysin [LSer-LSer-Gly-tri(5-JV-acetyl- -N-hydroxy-Orn)] (Norrestam et al, 1975) and ferrichrome (Loghry and van der Helm, 1978) have been determined and show that the molecules are essentially isostruc-tural. In these molecules, the ferric ion has approximate octahedral coordination to the six oxygen atoms of the three 5-N-acetyl-5-N-hydroxy or the 

3-HyPic-LThr-DAbu-LPro-LMePhe-4-oxo-LPip-LPhg  

---