Structural determinants of the unusual helix stability of a de novo engineered vascular endothelial growth factor (VEGF) mimicking peptide

The unusual thermal stability of a bioactive peptide, Ac-QK, which retains a high degree of helix structure at high temperature was investigated. The NMR structure of QK in pure water presents a central helical sequence, which corresponds to the VEGF N-terminal helix, flanked by N- and C-capping regions. The helical conformation of QK represents an important prerequisite for its biological activity, since the isolated peptide, corresponding to the helix region of VEGF, does not assume a helical conformation and does not have significant biological activity. The aggregation state of the peptide under conditions identical to those used in the NMR structure determination was confirmed by NMR DOSY experiments. The thermal behavior was also analyzed by CD spectroscopy which allowed to extend the temperature range from 278 to 368 K. NMR analysis of QKA10 showed at 298 K at 45% helicity decrease with respect to QK, and also indicated that at 343 K, QKA10 is in random conformation.