Vijayaraghavan R, Kumar P, Dey S, Singh T P
Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110 029, India.
J Pept Res. 2003 Aug;62(2):63-9. doi: 10.1034/j.1399-3011.2003.00071.x.
Highly specific structures can be designed by inserting dehydro-residues into peptide sequences. The conformational preferences of branched beta-carbon residues are known to be different from other residues. As an implication it was expected that the branched beta-carbon dehydro-residues would also induce different conformations when substituted in peptides. So far, the design of peptides with branched beta-carbon dehydro-residues at (i + 1) position has not been reported. It may be recalled that the nonbranched beta-carbon residues induced beta-turn II conformation when placed at (i + 2) position while branched beta-carbon residues induced beta-turn III conformation. However, the conformation of a peptide with a nonbranched beta-carbon residue when placed at (i + 1) position was not found to be unique as it depended on the stereochemical nature of its neighbouring residues. Therefore, in order to induce predictably unique structures with dehydro-residues at (i + 1) position, we have introduced branched beta-carbon dehydro-residues instead of nonbranched beta-carbon residues and synthesized two peptides: (I) N-Carbobenzoxy-DeltaVal-Ala-Leu-OCH3 and (II) N-Carbobenzoxy-DeltaIle-Ala-Leu-OCH3 with DeltaVal and DeltaIle, respectively. The crystal structures of peptides (I) and (II) have been determined and refined to R-factors of 0.065 and 0.063, respectively. The structures of both peptides were essentially similar. Both peptides adopted type II beta-turn conformations with torsion angles; (I): phi1 = -38.7 (4) degrees, psi1 = 126.0 (3) degrees; phi2 = 91.6 (3) degrees, psi2 = -9.5 (4) degrees and (II): phi1 = -37.0 (6) degrees, psi1 = 123.6 (4) degrees, phi2 = 93.4 (4), psi2 = -11.0(4) degrees respectively. Both peptide structures were stabilized by intramolecular 4-->1 hydrogen bonds. The molecular packing in both crystal structures were stabilized in each by two identical hydrogen bonds N1...O1' (-x, y + 1/2, -z) and N2...O2' (-x + 1, y + 1/2, -z) and van der Waals interactions.
通过将脱氢残基插入肽序列中，可以设计出高度特异性的结构。已知支链β-碳残基的构象偏好与其他残基不同。由此推测，当支链β-碳脱氢残基取代肽中的其他残基时，也会诱导出不同的构象。到目前为止，尚未有在（i + 1）位置带有支链β-碳脱氢残基的肽的设计报道。可以回想一下，非支链β-碳残基位于（i + 2）位置时会诱导出II型β-转角构象，而支链β-碳残基会诱导出III型β-转角构象。然而，当非支链β-碳残基位于（i + 1）位置时，肽的构象并非唯一，这取决于其相邻残基的立体化学性质。因此，为了在（i + 1）位置用脱氢残基诱导出可预测的独特结构，我们引入了支链β-碳脱氢残基而非非支链β-碳残基，并合成了两种肽：（I）N-苄氧羰基-Δ缬氨酸-丙氨酸-亮氨酸-OCH3和（II）N-苄氧羰基-Δ异亮氨酸-丙氨酸-亮氨酸-OCH3，分别含有Δ缬氨酸和Δ异亮氨酸。已确定并精修了肽（I）和（II）的晶体结构，其R因子分别为0.065和0.063。两种肽的结构基本相似。两种肽均采用II型β-转角构象，扭转角分别为：（I）：φ1 = -38.7（4）°，ψ1 = 126.0（3）°；φ2 = 91.6（3）°，ψ2 = -9.5（4）°；（II）：φ1 = -37.0（6）°，ψ1 = 123.6（4）°，φ2 = 93.4（4）°，ψ2 = -11.0（4）°。两种肽的结构均通过分子内4→1氢键得以稳定。两种晶体结构中的分子堆积均通过两个相同的氢键N1...O1'（-x，y + 1/2，-z）和N2...O2'（-x + 1，y + 1/2，-z）以及范德华相互作用得以稳定。
