Design of peptides with α,β-dehydro-residues:: synthesis, and crystal and molecular structure of 310-helical tetrapeptide BOC-L-Val-ΔPhe-ΔPhe-L-Ile-OCH3

The peptide Boc-L-Val-Delta Phe-Delta Phe-L-Ile-OCH3 was synthesized using the azlactone method in the solution phase, and its crystal and molecular structures were determined by X-ray diffraction. Single crystals were grown by slow evaporation from solution in methanol at 25 degrees C. The crystals belong to an orthorhombic space group P2(1)2(1)2(1) with a = 22.882(7) Angstrom, b = 15.430(5) Angstrom, c = 18.330(5) Angstrom and Z = 4. The structure was determined by direct methods and refined by a least-squares procedure to an R-value of 0.073. The peptide adopts a right-handed 3(10)-helical conformation with backbone torsion angles: phi(1) = 56.0(6)degrees, psi(1) = -38.0(6)degrees, phi(2) = -53.8(6)degrees, psi(2) = 23.6(6)degrees, phi(3) = -82.9(6)degrees, psi(3) = -10.6(7)degrees, phi(4) = 124.9(5)degrees. All the peptide bonds are trans. The conformation is stabilized by intramolecular 4-->1 hydrogen bonds involving Boc carbonyl oxygen and NH of Delta Phe(3) and CO of Val(1) and NH of Ile(4). it is noteworthy that the two other chemically very similar peptides: Boc-Val-Delta Phe-Delta Phe-Ala-OCH3 (i) and Boc-Val-Delta Phe-Delta Phe-Val-OCH3 (ii) with differences only at the fourth position have been found to adopt folded conformations with two overlapping beta-turns of types II and III', respectively, whereas the present peptide adopts two overlapping beta-turns of type III. Thus the introduction of lie at fourth position in a sequence Val-Delta Phe-Delta Phe-X results in the formation of a 3(10)-helix. The crystal structure is stabilized by intermolecular hydrogen bonds involving NH of Va(1) and carbonyl oxygen of a symmetry related (-x, y-1/2, 1/2 + z) Delta Phe(2) and NH of Delta Phe(2) with carbonyl oxygen of a symmetry related (x, y1/2, 1/2 + z) Ile(4). This gives rise to long columns of helical molecules linked head to tail running along [010] direction.