Lee Myung Kyu, Kim Hee Kyung, Lee Tae Young, Hahm Kyung-Soo, Kim Kil Lyong
Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, PO Box 115, Yusong, Daejeon 305-600, Korea.
Exp Mol Med. 2006 Feb 28;38(1):18-26. doi: 10.1038/emm.2006.3.
The constrained a-helical structure of a C-peptide is useful for enhancing anti-HIV-1 activity. The i and i+3 positions in an a-helical structure are located close together, therefore D-Cys (dC) and L-Cys (C) were introduced at the positions, respectively, to make a dC-C disulfide bond in 28mer C-peptides. Accordingly, this study tested whether a dC-C disulfide bond would increase the a-helicity and anti-HIV-1 activity of peptides. A C-peptide can be divided into three domains, the N-terminal hydrophobic domain (HPD), middle interface domain (IFD), and C-terminal hydrogen domain (HGD), based on the binding property with an N-peptide. In general, the dC-C modifications in HPD enhanced the anti-HIV-1 activity, while those in IFD and HGD resulted in no or much less activity. The modified peptides with no activity clearly showed much less a-helicity than the native peptides, while those with higher activity showed an almost similar or slightly increased alpha-helicity. Therefore, the present results suggest that the introduction of a dC-C bridge in the N-terminal hydrophobic domain of a C-peptide may be useful for enhancing the anti-HIV-1 activity.
C肽的受限α-螺旋结构有助于增强抗HIV-1活性。在α-螺旋结构中，i和i + 3位置彼此靠近，因此分别在这些位置引入D-半胱氨酸（dC）和L-半胱氨酸（C），以在28聚体C肽中形成dC-C二硫键。因此，本研究测试了dC-C二硫键是否会增加肽的α-螺旋度和抗HIV-1活性。根据与N肽的结合特性，C肽可分为三个结构域，即N端疏水结构域（HPD）、中间界面结构域（IFD）和C端氢结构域（HGD）。一般来说，HPD中的dC-C修饰增强了抗HIV-1活性，而IFD和HGD中的修饰则没有活性或活性大大降低。没有活性的修饰肽明显比天然肽的α-螺旋度低得多，而活性较高的修饰肽则显示出几乎相似或略有增加的α-螺旋度。因此，目前的结果表明，在C肽的N端疏水结构域中引入dC-C桥可能有助于增强抗HIV-1活性。
