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Solution conformation of the ferrichromes

1972; Elsevier BV; Volume: 68; Issue: 2 Linguagem: Inglês

10.1016/0022-2836(72)90213-6

1089-8638

Miguel Llinás, M. P. Klein, J. B. Neilands,

Chemical Synthesis and Analysis

Ferrichrome, ferricrocin, ferrichrysin and ferrichrome A are ferric cyclohexapeptides whose general primary composition is represented by where the Res2,3 sites are occupied by glycyl or l-seryl residues and Orn1,2,3 stands for δ-N-acyl-δ-N-hydroxy-l-ornithyl. The latter provide the hydroxamate ligands which co-ordinate the metal ion. The 220 MHz proton magnetic resonance spectra of Al3+ and Ga3+ chelates of the four homologous peptides in aqueous and in deutero-dimethylsulfoxide solutions are reported and analyzed in terms of the molecular conformations. In both solvents the chemical shifts of the amide proton resonances and their temperature dependences are consistent with a structure containing two transannular hydrogen bonds, as in the Schwyzer model for cyclohexapeptides. The metal ion enforces the structure of the peptide backbone; thus, the reported conformational differences resulting from residue substitutions at sites 2 and 3, as well as from solvation effects, are virtually eliminated upon its binding. The chelates exhibit pronounced chemical shift differences among the amide NH's with markedly reduced temperature dependences for four of them. Gross amide hydrogendeuterium exchange kinetics in 2H2O indicates that these four amides have a highly diminished interaction with the solvent. The comparative spectra of the analogous chelates permits unequivocal assignments of all proton resonances to residues in the absolute sequence. The magnitude of the amide NHCaH spin-spin couplings yields estimates of the conformational φ dihedral angles. Aside from slight seryl side-chain solvation pressures, the proton magnetic resonance data for the chelates in solution are in good agreement with the static X-ray crystallographic model for ferrichrome A.