Structural Characterization of Histatin 5-Spermidine Conjugates: A Combined Experimental and Theoretical Study

Histatin 5 (Hst5) is a naturally occurring antimicrobial peptide that acts as the first line of defense against oral candidiasis. It has been shown that conjugation of the active Hst5 fragment, Hst5_4-15, and the polyamine spermidine (Spd) improves the candidacidal effect. Knowledge about the structure of these conjugates is, however, very limited. Thus, the aim of this study was to characterize the structural properties of the Hst5_4-15-Spd conjugates by performing atomistic molecular dynamics simulations in combination with small-angle X-ray scattering. It was shown that the Hst5_4-15-Spd conjugates adopt extended and slightly rigid random coil conformations without any secondary structure in aqueous solution. It is hypothesized that the increased fungal killing potential of Hst5_4-15-Spd, in comparison with the Spd-Hst5_4-15 conjugate, is due to the more extended conformations of the former, which cause the bonded Spd molecule to be more accessible for recognition by polyamine transporters in the cell.