Development of a series of cross-linking agents that effectively stabilize alpha-helical structures in various short peptides.
A series of cross-linking agents of varying rigidity and length were designed to stabilize helical structures in short peptides and were then synthesized. The sequences of the short peptides employed in this study each include two X residues (X=Dap, Dab, Orn, and Lys) at the i/i+4, i/i+7, or i/i+11 positions to provide the sites for cross-linking. These peptides were subjected to reaction with the synthesized cross-linking agents, and the helical content of the resulting cross-linked peptides were analyzed in detail by circular dichroism. For each of the peptide classes we found combinations with the cross-linking agents suitable for the construction of stable helical structures up to >95 % helicity at 5 degrees C. Our method could also be applied to biologically related sequences seen in native proteins such as Rev.
Fujimoto
Kazuhisa
K
Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan. fujimoto@pha.u-toyama.ac.jp
Kajino
Masaoki
M
Inouye
Masahiko
M
D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry* / Q000187:drug effects* / Q000302:isolation & purification; D017433:Protein Structure, Secondary
D003432:Cross-Linking Reagents; D010455:Peptides