The constrained alpha-helical structure of a C-peptide is useful for enhancing anti-HIV-1 activity. The i and i+3 positions in an alpha-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 alpha-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 alpha-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.
Amino Acid Sequence ; Anti-HIV Agents/chemical synthesis/*chemistry/isolation & purification/*pharmacology ; Cell Line ; Circular Dichroism ; Cysteine/chemistry ; Disulfides/chemistry ; HIV Envelope Protein gp41/*chemistry ; HIV-1/*drug effects/growth & development ; Humans ; Inhibitory Concentration 50 ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemical synthesis/*chemistry/isolation & purification/*pharmacology ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Research Support, Non-U.S. Gov't ; Structure-Activity Relationship

While introducing the indications of low-density lipoprotein (LDL) apheresis, LDL absorption systems were reviewed generally. As the key components for binding LDL, four kinds of ligands which are synthesized by different principles are: 1. Positively charged peptides designed according to state charge force between ligand and LDL; 2. Peptides designed according to structural characteristics of the binding site between LDL and its receptors; 3. Antibody of Lp (a) obtained by immunizing mammals with designed peptides with the characteristics of Lp (a); 4. Segments of LDL binding proteins (LBPs) synthesized with genetic engineering method based on the specific binding of LBPs to LDL. Requirements of matrices carrying these ligands are also considered. Finally, future developments in treatments of familial hypercholesterolemia by means of blood purification using synthesized peptides are overlooked.
Adsorption ; Drug Carriers ; Drug Design ; Female ; Hemoperfusion ; instrumentation ; methods ; Humans ; Hyperlipoproteinemia Type II ; blood ; therapy ; Ligands ; Lipoproteins, LDL ; blood ; isolation & purification ; Male ; Peptides ; chemical synthesis ; therapeutic use ; Receptors, LDL ; chemistry