K. R. Rajashankar

Role of two consecutive α,β-dehydrophenylalanines in peptide structure: crystal and molecular structure of Boc-Leu-ΔPhe-ΔPhe-Ala-Phe-NHMe

An Nα‐protected model pentapeptide containing two consecutive ΔPhe residues, Boc‐Leu‐ΔPhe‐ΔPhe‐Ala‐Phe‐NHMe, has been synthesized by solution methods and fully characterized. 1H‐nmr studies provided evidence for the occurrence of a significant population of a conformer having three consecutive, intramolecularly H‐bonded β‐bends in solution. The solid state structure has been determined by x‐ray diffraction methods. The crystals grown from aqueous methanol are orthorhombic, space group P212121, a = 11.503(2), b = 16.554(2), c = 22.107(3) Å, V = 4209(1) Å,3 and Z = 4. The x‐ray data were collected on a CAD4 diffractometer using CuKa radiation (λ = 1.5418 Å). The structure was determined using direct methods and refined by full‐matrix least‐squares procedure. The R factor is 5.3%. The molecule is characterized by a right handed 310‐helical conformation (〈ϕ〉 = −68.2°, 〈ψ〉 = −26.3°), which is made up of two consecutive type III β‐bends and one type I β‐bend. In the solid state the helical molecules are aligned head‐to‐tail, thus forming long rod like structures. A comparison with other peptide structures containing consecutive ΔPhe residues is also provided. The present study confirms that the ‐ΔPhe‐ΔPhe‐sequence can be accommodated in helical structures.

Helix termination and chain reversal: crystal and molecular structure of the alpha, beta-dehydrooctapeptide Boc-Val-DeltaPhe-Phe-Ala-Leu-Ala-DeltaPhe-Leu-OH.

The crystal structure of the dehydro octapeptide Boc-Val-DeltaPhe-Phe-Ala-Leu-Ala-DeltaPhe-Leu-OH has been determined to atomic resolution by X-ray crystallographic methods. The crystals grown by slow evaporation of peptide solution in methanol/water are orthorhombic, space group P2(1)2(1)2(1). The unit cell parameters are a= 8.404(3), b= 25.598(2) and c= 27.946(3) Angstrom, Z=4. The agreement factor is R = 7.58% for 3636 reflections having (vertical bar Fo vertical bar) > or = 3sigma (vertical bar Fo vertical bar). The peptide molecule is characterised by a 3(10)-helix at the N-terminus and a pi-turn at the C-terminus. This conformation is exactly similar to the helix termination features observed in proteins. The pi-turn conformation observed in the octapeptide is in good agreement with the conformational features of pi-turns seen in some proteins. The alphaL-position in the pi-turn of the octapeptide is occupied by DeltaPhe7, which shows that even bulky residues can be accommodated in this position of the pi-turns. In proteins, it is generally seen that alphaL-position is occupied by glycine residue. No intermolecular head-to-tail hydrogen bonds are observed in solid state structure of the octapeptide. A water molecule located in the unit cell of the peptide molecule is mainly used to hold the peptide molecule together in the crystal. The conformation observed for the octapeptide might be useful to understand the helix termination and chain reversal in proteins and to construct helix terminators for denovo protein design.