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.
Ramalingam
K
K
Department of Oral Biology, State University of New York at Buffalo 14214, USA.
Gururaja
T L
TL
Ramasubbu
N
N
Levine
M J
MJ
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy; D002942:Circular Dichroism; D006801:Humans; D008825:Miconazole / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology*; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000494:pharmacology; D012984:Software; D000099053:Histidine-Rich Glycoprotein
D000935:Antifungal Agents; D010446:Peptide Fragments; D011506:Proteins; D012471:Salivary Proteins and Peptides; D000099053:Histidine-Rich Glycoprotein; D008825:Miconazole