Vijayaraghavan R, Kumar P, Dey S, Singh T P
Department of Biophysics, All India Institute of Medical Sciences, New Delhi.
J Pept Res. 1998 Aug;52(2):89-94. doi: 10.1111/j.1399-3011.1998.tb01362.x.
The dehydro-peptide Boc-L-Ile-deltaPhe-L-Trp-OCH3 was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P2(1)2(1)2(1)with a = 10.777(2), b = 11.224(2), c = 26.627(10) A. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [I > or = 2delta(I)]. The peptide failed to adopt a folded conformation with backbone torsion angles: phi1 = 90.8(8)degrees, psi1 = -151.6(6)degrees, phi2 = 89.0(8)degrees, psi2 = 15.9(9)degrees, phi3 = 165.7(7)degrees, psi3T = -166.0(7)degrees . A general rule derived from earlier studies indicates that a three-peptide unit sequence with a deltaPhe at the (i + 2) position adopts a beta-turn II conformation. Because the branched beta-carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the deltaPhe residue differently to generate a unique set of conformations in such peptides. The presence of beta-branched residues simultaneously at both (i + 1) and (i + 3) positions induces unfolded conformations in tetrapeptides, but a beta-branched residue substituted only at (i + 3) position can not prevent the formation of a folded beta-turn II conformation. On the other hand, the present structure shows that a beta-branched residue substituted at the (i + 1) position prevents the formation of a beta-turn II conformation. These observations indicate that a beta-branched residue at the (i + 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i + 3) position. This may be because of the trans disposition of the planar deltaPhe side-chain with respect to the C=O group in the residue. The molecules are packed in an anti-parallel manner to generate N2-H2...O2 (-x, y -1/2, -z + 3/2) and N3epsilon1-H3epsilon1 ...O1(-X, y -1/2, -z + 3/2) hydrogen bonds.
通过溶液相中的氮杂环丙烷方法合成了脱氢肽Boc-L-Ile-δPhe-L-Trp-OCH₃。该肽从甲醇中结晶，属于正交晶系空间群P2(1)2(1)2(1)，a = 10.777(2)，b = 11.224(2)，c = 26.627(10) Å。通过直接法确定了其结构，并对3093个观测反射[I≥2δ(I)]进行精修，R值为0.069。该肽未能采用具有主链扭转角的折叠构象：φ1 = 90.8(8)°，ψ1 = -151.6(6)°，φ2 = 89.0(8)°，ψ2 = 15.9(9)°，φ3 = 165.7(7)°，ψ3T = -166.0(7)°。从早期研究得出的一般规则表明，在(i + 2)位置具有δPhe的三肽单元序列采用β-转角II构象。由于缬氨酸和异亮氨酸等支链β-碳残基具有强烈的构象偏好，它们与δPhe残基的结合方式不同，从而在这类肽中产生独特的构象集。在(i + 1)和(i + 3)位置同时存在β-支链残基会导致四肽形成未折叠构象，但仅在(i + 3)位置取代的β-支链残基不能阻止折叠的β-转角II构象的形成。另一方面，目前的结构表明，在(i + 1)位置取代的β-支链残基会阻止β-转角II构象的形成。这些观察结果表明，在(i + 1)位置的β-支链残基会阻止折叠构象的形成，而在(i + 3)位置则不会产生相同程度的影响。这可能是由于平面δPhe侧链相对于残基中C=O基团的反式排列。分子以反平行方式堆积，形成N2-H2...O2 (-x, y -1/2, -z + 3/2)和N3ε1-H3ε1...O1(-X, y -1/2, -z + 3/2)氢键。
