A sequence preference for nucleation of α‐helix—crystal structure of Gly‐ L ‐Ala‐ L ‐Val and Gly‐ L ‐Ala‐ L ‐Leu: Some comments on the geometry of leucine zippers

The synthetic peptide Gly‐ L ‐Ala‐ L ‐Val (C 10 H 19 N 3 O 4 ·3H 2 O; GAV) crystallizes in the monoclinic space group P2 1 , with a = 8.052(2), b = 6.032(2), c = 15.779(7) Å, β = 98.520(1)°, V = 757.8 Å 3 , D x = 1.312 g cm −3 , and Z = 2. The peptide Gly‐ L ‐Ala‐ L ‐Leu (C 11 H 21 N 3 O 4 ·3H 2 O; GAL) crystallizes in the orthorhombic space group P2 1 2 1 2 1 , with a = 6.024(1), b = 8.171(1), c = 32.791(1) Å, V = 1614 Å 3 , D x = 1.289 g cm −3 , and Z = 4. Their crystal structures were solved by direct methods using the program SHELXS‐86, and refined to an R index of 0.05 for 1489 reflections for GAV and to an R index of 0.05 for 1563 reflections for GAL. The tripeptides exist as a zwitterion in the crystal and assume a near α‐helical backbone conformation with the following torsion angles: ψ 1 = −150.7°; ϕ 2 , ψ 2 = −68.7°, −38.1°; ϕ 3 , ψ 31 , ψ 32 , = −74.8°, −44.9°, 135.9° for GAV; ψ 1 = −150.3°; ϕ 2 , ψ 2 = −67.7°, −38.9°; ϕ 3 , ψ 31 , ψ 32 = −72.2°, −45.3°, 137.5°, for GAL. Both the peptide units in both of the tripeptides show significant deviation from planarity [ω 1 = −171.3(6)° and ω 2 = −172.0(6)° for GAV; ω 1 = −171.9(5)° and ω 2 = −173.2(6)° for GAL]. The sidechain conformational angles χ 21 and χ 22 are −61.7(5)° and 175.7(5)°, respectively, for valine, and the side‐chain conformations χ 12 and χ 23 's are −68.5(5)° and (−78.4(6)°, 159.1(5)°) respectively, for leucine. Each of the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH   3 +and COO − groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an α‐helix.