Lanthanide(III) complexes with two hexapeptides incorporating unnatural chelating amino acids: secondary structure and stability.
Unnatural metal-chelating amino acids bearing aminodiacetate side-chains have been introduced into two hexapeptides to obtain efficient lanthanide-binding peptides. The synthesis of the enantiopure Fmoc-Ada(n)(tBu)2-OH synthons is described with overall yields of 32 and 50% for n=2 and n=3 side-chain carbon atoms, respectively. The two peptides AcWAda(n)PGAda(n)GNH2 (Pn) were synthesized from the protected synthons by standard solid-phase peptide synthesis. Studies of the lanthanide complexes of the two peptides Pn by luminescence titrations, mass spectrometry, circular dichroism, and solution NMR spectroscopy demonstrate that the Ada(n) chain length has a dramatic effect on the complexation properties. Indeed, the flexible compound P3 forms a mononuclear complex of moderate stability (beta11=10(9.9)), which tends to transform into a binuclear species in the presence of excess of the metal ion. Interestingly, the more compact peptide P2 provides stable Ln3+ complexes with the exclusive formation of the mononuclear LnP2 adduct. The stability constant of TbP2 is two orders of magnitude higher (beta11=10(12.1)) than that measured for P3. The 800 MHz NMR spectrum of the La3+ complex of P2 evidences a well-defined type II beta-turn as well as a hydrophobic Trp(indole)-Pro interaction. These interactions exemplify the non-innocent character of the peptide spacer in the complex LaP2 as well as the role of a peptide secondary structure in the stabilization of metal complexes.
Cisnetti
Federico
F
INAC, Service de Chimie Inorganique et Biologique (UMR E 3 CEA UJF, FRE CNRS 3200), Commissariat à l'Energie Atomique, 17 rue des martyrs, 38054 Grenoble Cedex, France.
Gateau
Christelle
C
Lebrun
Colette
C
Delangle
Pascale
P
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008667:Metalloproteins / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary
D000596:Amino Acids; D028581:Lanthanoid Series Elements; D008667:Metalloproteins; D010455:Peptides