Effects of hydrogen-bond deletion on peptide helices: structural characterization of depsipeptides containing lactic acid.
The insertion of alpha-hydroxy acids into peptide chains provides a convenient means for investigating the effects of hydrogen bond deletion on polypeptide secondary structures. The crystal structures of three oligopeptides containing L-lactic acid (Lac) residue have been determined. Peptide 1, Boc-Val-Ala-Leu-Aib-Val-Lac-Leu-Aib-Val-Ala-Leu-OMe (Boc: tert-butyloxycarbonyl; Aib: alpha- aminoisobutyric acid; OMe: methyl ester), and peptide 2, Boc-Val-Ala-Leu-Aib-Val-Lac-Leu-Aib-Val-Leu-OMe, adopt completely helical conformations in the crystalline state with the Lac(6) residue comfortably accommodated in the center of a helix. The distance between the O atoms of Leu(3) CO group and the Lac(6) O (ester) in both the structures is 3.1-3.3 A. The NMR and CD studies of peptide 1 and its all-amide analogue 4, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe, provide firm evidence for a continuous helical conformation in solution in both the cases. In a 14-residue peptide 3, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Val-Ala-Leu-Aib-Val-Lac-Leu-OMe, residues Val(1)-Leu(10) adopt a helical conformation. Aib(11) is the site of chiral reversal resulting in helix termination by formation of a Schellman motif. Residues 12-14 adopt nonhelical conformations. The loss of the hydrogen bond near the C-terminus appears to facilitate the chiral reversal at Aib(11). Published 2001 John Wiley & Sons, Inc. Biopolymers 59: 276-289, 2001
Karle
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Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, DC, 20375-5341, USA.
Das
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Balaram
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D000595:Amino Acid Sequence; D001704:Biopolymers / Q000737:chemistry; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D019344:Lactic Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions
D001704:Biopolymers; D009842:Oligopeptides; D012996:Solutions; D019344:Lactic Acid