Anticandida activity is retained in P-113, a 12-amino-acid fragment of histatin 5.
Through the analysis of a series of 25 peptides composed of various portions of the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of histatin 5, as the smallest fragment that retains anticandidal activity comparable to that of the parent compound. Amidation of the P-113 C terminus increased the anticandidal activity of P-113 approximately twofold. The three histidine residues could be exchanged for three hydrophobic residues, with the fragment retaining anticandidal activity. However, the change of two or more of the five basic (lysine and arginine) residues to uncharged residues resulted in a substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P-113D, was as active against Candida albicans as the L-amino-acid form. In vitro MIC tests in low-ionic-strength medium showed that P-113 has potent activity against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. These results identify P-113 as a potential antimicrobial agent in the treatment of oral candidiasis.
Rothstein
D M
DM
Periodontix, Inc., Watertown, Massachusetts, USA. drothstein@rcn.com
Spacciapoli
P
P
Tran
L T
LT
Xu
T
T
Roberts
F D
FD
Dalla Serra
M
M
Buxton
D K
DK
Oppenheim
F G
FG
Friden
P
P
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D054808:Histatins; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*; D012504:Saralasin / Q000737:chemistry / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
D000935:Antifungal Agents; C068075:HTN3 protein, human; D054808:Histatins; D010446:Peptide Fragments; D012471:Salivary Proteins and Peptides; D012504:Saralasin