Hossain M B, Van Der Helm D, Antel J, Sheldrick G M, Weinheimer A J, Sanduja S K
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, USA.
Int J Pept Protein Res. 1996 Jan-Feb;47(1-2):20-7. doi: 10.1111/j.1399-3011.1996.tb00805.x.
The molecular structure of didemnin A, the parent compound of a series of antiviral cytotoxic depsipeptides extracted from a marine tunicate Trididemnum solidum of the family of Didemnidae, has been determined by single-crystal X-ray diffraction. In the crystal, didemnin A molecules form pseudo-symmetric dimeric pair. The two molecules in the dimer are held together by strong N--H center dot center dot center dot O and N--H center dot center dot center dot N hydrogen bonds. A chloride ion, placed almost symmetrically between the dimeric pair, forms N--H center dot center dot center dot Cl hydrogen bonds (3.19 and 3.23 Angstrom) with both the molecules. The two independent molecules in the structure have closely similar geometry. For each molecule, the 23-membered depsipeptide ring assumes a folded conformation in the shape of a 'bent figure-of-eight' similar to that observed in the didemnin B crystal structure. The major conformational differences in the macrocycle of didemnin A and didemnin B are around the Hip residue. The root mean-square (RMS) difference of 20 of the 23 endocyclic torsion angles for the two structures is less than 10 degrees, while the three bond torsions in the Hip residue vary by about 50 degrees. The macrocycle conformation is stabilized by a transannular N--H center dot center dot center dot O hydrogen bond linking the isostatine amide group with the leucine carbonyl group. The truncated linear chain is folded back toward the macrocyclic ring and is held by a N--H center dot center dot center dot O hydrogen bond between the leucine amide group and Me-Leu carbonyl group. The transannular hydrogen bond in the didemnin A structure (N4--H center dot center dot center dot O3 = 2.83 Angstrom in both molecule a and molecule b) is noticeably stronger than that observed in the didemnin B structure (3.02 Angstrom). The X-ray structure of didemnin A is generally consistent with that obtained by NMR studies. Within the crystal, the molecules are packed in zig-zag chains formed by intermolecular O--H center dot center dot center dot O hydrogen bonds. The crystal structure and packing of didemnin A are quite different from that of the didemnin B structure.
从Didemnidae科的海洋被囊动物Trididemnum solidum中提取的一系列具有抗病毒细胞毒性的缩肽的母体化合物didemnin A的分子结构，已通过单晶X射线衍射确定。在晶体中，didemnin A分子形成假对称二聚体对。二聚体中的两个分子通过强N--H···O和N--H···N氢键结合在一起。一个氯离子几乎对称地位于二聚体对之间，与两个分子都形成N--H···Cl氢键（3.19和3.23埃）。结构中的两个独立分子具有非常相似的几何形状。对于每个分子，23元缩肽环呈现出类似于在didemnin B晶体结构中观察到的“弯曲8字形”的折叠构象。didemnin A和didemnin B大环的主要构象差异围绕着Hip残基。两种结构的23个内环扭转角中的20个的均方根（RMS）差异小于10度，而Hip残基中的三个键扭转变化约50度。大环构象通过连接异亮氨酸酰胺基团和亮氨酸羰基的跨环N--H···O氢键得以稳定。截短的线性链向大环环回折，并通过亮氨酸酰胺基团和甲基亮氨酸羰基之间的N--H···O氢键固定。didemnin A结构中的跨环氢键（分子a和分子b中的N4--H···O3 = 2.83埃）明显强于在didemnin B结构中观察到的氢键（3.02埃）。didemnin A的X射线结构与通过核磁共振研究获得的结构总体一致。在晶体内，分子通过分子间O--H···O氢键堆积成锯齿链。didemnin A的晶体结构和堆积与didemnin B结构有很大不同。
