Abstract
Although the peptide Boc-Aib1-Ala2-Leu3-Aib4-Ala5-Leu6-Aib7-Ala8-L eu9-Aib10-OME [with a t-butoxycarbonyl (Boc) blocking group at the amino terminus, a methyl ester (OMe) at the carboxyl terminus, and four alpha-amino-isobutyric (Aib) residues] has a 3-fold repeat of residues, the helix formed by the peptide backbone is irregular. The carboxyl-terminal half assumes an alpha-helical form with torsion angles phi and psi of approximately -60 degrees and -45 degrees, respectively, whereas the amino-terminal half is distorted by an insertion of a water molecule between the amide nitrogen of Ala5 [N(5)] and the carbonyl oxygen of Ala2 [O(2)]. The water molecule W(1) acts as a bridge by forming hydrogen bonds N(5)...W(1) (2.93 A) and W(1)...O(2) (2.86 A). The distortion of the helix exposes the carbonyl oxygens of Aib1 and Aib4 to the outside environment, with the consequence that the helix assumes an amphiphilic character despite having all apolar residues. Neighboring helices in the crystal run in antiparallel directions. On one side of a helix there are only hydrophobic contacts with efficient interdigitation of leucine side chains with those from the neighboring helix. On the other side of the helix there are hydrogen bonds between protruding carbonyl oxygens and four water molecules that separate two neighboring helices. Along the helix axis the helices bind head-to-tail with a direct hydrogen bond N(2)...O(9) (3.00 A). Crystals grown from methanol/water solution are in space group P21 with a = 15.778 +/- 0.004 A, b = 11.228 +/- 0.002 A, c = 18.415 +/- 0.003 A, beta = 102.10 +/- 0.02 degrees, and two formula units per cell for C49H88N10O13.2H2O.CH3OH. The overall agreement factor R is 7.5% for 3394 reflections observed with intensities greater than 3 sigma (F), and the resolution is 0.90 A.
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Selected References
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