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Design of Peptides Using α,β‐Dehydro‐residues: Synthesis, Crystal Structure and Molecular Conformation of N ‐Boc‐ L ‐Val‐ΔPhe–ΔPhe‐ L ‐Ala‐OCH 3

1996; Wiley; Volume: 2; Issue: 6 Linguagem: Inglês

10.1002/psc.77

1099-1387

Smita Bhatia, Sharmistha Dey, Punit Kaur, T.P. Singh,

Antimicrobial Peptides and Activities

Abstract To obtain general rules of peptide design using α,β‐dehydro‐residues, a sequence with two consecutive ΔPhe‐residues, Boc‐ L ‐Val‐ΔPhe–ΔPhe‐ L ‐Ala‐OCH 3 , was synthesized by azlactone method in solution phase. The peptide was crystallized from its solution in an acetone/water mixture (70:30) in space group P6 1 with a = b =14.912(3) Å, c = 25.548(5) Å, V =4912.0(6) Å 3 . The structure was determined by direct methods and refined by a full matrix least‐squares procedure to an R value of 0.079 for 2891 observed [ I ⩾3σ( I )] reflections. The backbone torsion angles ϕ 1 =−54(1)°, ψ 1 = 129(1)°, ω 1 =−177(1)°, ϕ 2 =57(1)°, ψ 2 =15(1)°, ω 2 =−170(1)°, ϕ 3 =80(1)°, ψ 3 =7(2)°, ω 3 =−177(1)°, ϕ 4 =−108(1)° and ψ T 4 =−34 (1)° suggest that the peptide adopts a folded conformation with two overlapping β‐turns of types II and III′. These turns are stabilized by two intramolecular hydrogen bonds between the CO of the Boc group and the NH of ΔPhe 3 and the CO of Val 1 and the NH of Ala 4 . The torsion angles of ΔPhe 2 and ΔPhe 3 side chains are similar and indicate that the two ΔPhe residues are essentially planar. The folded molecules form head‐to‐ tail intermolecular hydrogen bonds giving rise to continuous helical columns which run parallel to the c‐axis. This structure established the formation of two β‐turns of types II and III′ respectively for sequences containing two consecutive ΔPhe residues at ( i +2) and ( i +3) positions with a branched β‐carbon residue at one end of the tetrapeptide.