Gauba Varun, Hartgerink Jeffrey D
Department of Chemistry, Rice University, 6100 Main Street, Mail Stop 60, Houston, TX 77005, USA.
J Am Chem Soc. 2007 Mar 7;129(9):2683-90. doi: 10.1021/ja0683640. Epub 2007 Feb 13.
Collagen, a fibrous protein, is an essential structural component of all connective tissues such as cartilage, bones, ligaments, and skin. Type I collagen, the most abundant form, is a heterotrimer assembled from two identical alpha1 chains and one alpha2 chain. However, most synthetic systems have addressed homotrimeric triple helices. In this paper we examine the stability of several heterotrimeric collagen-like triple helices with an emphasis on electrostatic interactions between peptides. We synthesize seven 30 amino acid peptides with net charges ranging from -10 to +10. These peptides were mixed, and their ability to form heterotrimers was assessed. We successfully show the assembly of five different AAB heterotrimers and one ABC heterotrimer. The results from this study indicate that intermolecular electrostatic interactions can be utilized to direct heterotrimer formation. Furthermore, amino acids with poor stability in collagen triple helices can be "rescued" in heterotrimers containing amino acids with known high triple helical stability. This mechanism allows collagen triple helices to have greater chemical diversity than would otherwise be allowed.
胶原蛋白是一种纤维蛋白，是所有结缔组织（如软骨、骨骼、韧带和皮肤）的重要结构成分。I型胶原蛋白是最丰富的形式，是由两条相同的α1链和一条α2链组装而成的异源三聚体。然而，大多数合成系统研究的是同三聚体三螺旋。在本文中，我们研究了几种异源三聚体类胶原蛋白三螺旋的稳定性，重点关注肽之间的静电相互作用。我们合成了七种净电荷范围从-10到+10的30个氨基酸的肽。将这些肽混合，并评估它们形成异源三聚体的能力。我们成功展示了五种不同的AAB异源三聚体和一种ABC异源三聚体的组装。这项研究的结果表明，分子间静电相互作用可用于指导异源三聚体的形成。此外，在胶原蛋白三螺旋中稳定性较差的氨基酸可以在含有已知高三螺旋稳定性氨基酸的异源三聚体中“得到挽救”。这种机制使胶原蛋白三螺旋具有比其他情况更大的化学多样性。
