Laboratory of Organic Chemistry, D-CHAB, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
J Am Chem Soc. 2012 Oct 17;134(41):17117-24. doi: 10.1021/ja3066418. Epub 2012 Oct 2.
The effect of sterically demanding groups at proline residues on the conformational stability of the collagen triple helix was examined. The thermal stabilities (T(m) and ΔG) of eight different triple helices derived from collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were determined and served as a relative measure for the conformational stability of the corresponding collagen triple helices. The results show that sterically demanding substituents are tolerated in the collagen triple helix when they are attached to (4R)-configured amidoprolines in the Xaa position or to (4S)-configured amidoprolines in the Yaa position. Structural studies in which the preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid with the Pro and Hyp residues within a crystal structure of collagen revealed that the sterically demanding groups point to the outside of these two triple helices and thereby do not interfere with the formation of the triple helix. In all of the other examined collagen derivatives with lower stability of the triple helices, the acetyl or pivaloyl residues point toward the inside of the triple helix and clash with a residue of the neighboring strand. The results also revealed that unfavorable steric dispositions affect the conformational stability of the collagen triple helix more than unfavorable ring puckers of the proline residues. The results are useful for the design of functionalized collagen based materials.
研究了脯氨酸残基中空间位阻基团对胶原蛋白三螺旋结构构象稳定性的影响。测定了来自胶原模型肽的 8 种不同三螺旋的热稳定性（Tm 和ΔG），这些模型肽中的酰胺脯氨酸具有（4R）或（4S）构型，并且在 Xaa 或 Yaa 位置带有甲基或更大的叔丁基取代基，这些取代基作为相应胶原蛋白三螺旋构象稳定性的相对度量。结果表明，当空间位阻取代基连接到 Xaa 位置的（4R）构型酰胺脯氨酸或 Yaa 位置的（4S）构型酰胺脯氨酸时，它们可以在胶原蛋白三螺旋中被容忍。结构研究表明，在胶原蛋白晶体结构中，（4R）或（4S）构型酰胺脯氨酸的优先构象与 Pro 和 Hyp 残基重叠，结果表明，这些空间位阻基团指向这两个三螺旋的外侧，因此不会干扰三螺旋的形成。在所有其他研究的胶原蛋白衍生物中，三螺旋的稳定性较低，乙酰基或特戊酰基残基指向三螺旋的内侧，与相邻链的残基发生冲突。结果还表明，不利的空间位阻排列比脯氨酸残基的不利的环褶皱更能影响胶原蛋白三螺旋的构象稳定性。这些结果对于设计基于功能性胶原蛋白的材料很有用。
