Stabilization of helix by side-chain interactions in histatin-derived peptides: role in candidacidal activity

Candida albicans is an opportunistic pathogen prevalent in AIDS patients and oral candidiasis. Azolebased drugs are currently used in the treatment of candidiasis. Histidine-rich peptides (histatins), are the natural inhibitors of candida species present in human salivary secretions. Sequence comparison of histatins revealed the common motif--KRKFHE--in active peptide fragments. Molecular modeling analysis showed structural similarity between this segment of histatins and azole-based drugs. The helical conformation adopted by histatin-5 may be stabilized by two side chain-side chain interactions (Phe... His and Arg ... Glu). Based on sequence comparison of histatin peptides and molecular modeling, a synthetic 10-residue peptide derived from histatin-5 was helical and possessed significant anti candida activity. This peptide may be used as a template to develop histatin-based drugs for treating oral candidiasis.