Metal clips that induce unstructured pentapeptides to be alpha-Helical in water

Ma, Michelle T., Hoang, Huy N., Scully, Conor C. G., Appleton, Trevor G. and Fairlie, David P. (2009) Metal clips that induce unstructured pentapeptides to be alpha-Helical in water. Journal of the American Chemical Society, 131 12: 4505-4512. doi:10.1021/ja900047w

Author Ma, Michelle T.
Hoang, Huy N.
Scully, Conor C. G.
Appleton, Trevor G.
Fairlie, David P.
Title Metal clips that induce unstructured pentapeptides to be alpha-Helical in water
Formatted title
Metal clips that induce unstructured pentapeptides to be α-Helical in water
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
Publication date 2009-04-01
Year available 2009
Sub-type Article (original research)
DOI 10.1021/ja900047w
Volume 131
Issue 12
Start page 4505
End page 4512
Total pages 8
Editor Peter J. Stang
Place of publication Washington , DC, U.S.A.
Publisher American Chemical Society
Collection year 2010
Language eng
Subject C1
8608 Human Pharmaceutical Products
860899 Human Pharmaceutical Products not elsewhere classified
0399 Other Chemical Sciences
Formatted abstract
Short peptides corresponding to protein helices do not form thermodynamically stable helical structures in water, a solvent that strongly competes for hydrogen-bonding amides of the peptide backbone. Metalloproteins often feature metal ions coordinated to amino acids within hydrogen-bonded helical regions of protein structure, so there is a prospect of metals stabilizing or inducing helical structures in short peptides. However, this has only previously been observed in nonaqueous solvents or under strongly helix-favoring conditions in water. Here cis-[Ru(NH3)4(solvent)2]2+ and [Pd(en)(solvent)2]2+ are compared in water for their capacity as metal clips to induce α-helicity in completely unstructured peptides as short as five residues, Ac-HARAH-NH2 and Ac-MARAM-NH2. More α-helicity was observed for the latter pentapeptide and, when chelated to ruthenium, it showed the greatest α-helicity yet reported for a short metallopeptide in water ~80%). Helicity was clearly induced rather than stabilized, and the two methionines were 1013-fold more effective than two histidines in stabilizing the lower oxidation state Ru(II) over Ru(III). The study identifies key factors that influence stability of an α-helical turn in water, suggests metal ions as tools for peptide folding, and raises an intriguing possibility of transiently coordinated metal ions playing important roles in native folding of polypeptides in water.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Thu, 03 Sep 2009, 08:20:47 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience