Metal clips induce folding of a short unstructured peptide into an alpha-helix via turn conformations in water. Kinetic versus thermodynamic products.
Short peptides corresponding to two to four alpha-helical turns of proteins are not thermodynamically stable helices in water. Unstructured octapeptide Ac-His1-Ala2-Ala3-His4-His5-Glu6-Leu7-His8-NH(2) (1) reacts with two [Pd((15)NH(2)(CH(2))(2)(15)NH(2))(NO(3))(2)] in water to form a kinetically stable intermediate, [[Pden](2)[(1,4)(5,8)-peptide]](2), in which two 19-membered metallocyclic rings stabilize two peptide turns. Slow subsequent folding to a thermodynamically more stable two-turn alpha-helix drives the equilibrium to [[Pden](2)[(1,5)(4,8)-peptide]] (3), featuring two 22-membered rings. This transformation from unstructured peptide via turns to an alpha-helix suggests that metal clips might be useful probes for investigating peptide folding.
Beyer
Renée L
RL
Centre for Drug Design and Development, Institute for Molecular Bioscience, and Department of Chemistry, School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Qld 4072, Australia.
Hoang
Huy N
HN
Appleton
Trevor G
TG
Fairlie
David P
DP
D002942:Circular Dichroism; D007700:Kinetics; D008667:Metalloproteins / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011522:Protons; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D008667:Metalloproteins; D009842:Oligopeptides; D009942:Organometallic Compounds; D011522:Protons; D012996:Solutions; D014867:Water; D010165:Palladium