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New peptide holds promise as antifungal agent
By LOIS BAKER
Contributing Editor
Searching for better treatments for oral infections that plague persons with compromised immune systems, UB oral biologists have developed a novel peptide that appears to be a good candidate for treating candidiasis and other fungal conditions.
Candidiasis is a common fungal infection in persons undergoing chemotherapy or organ transplantation, or those infected with HIV.
"We wanted to develop an antifungal agent that would have fewer side effects than current treatments," said Libuse Bobek, professor of oral biology in the School of Dental Medicine and senior author on the study.
"We found that a peptide called MUC7 12-mer-D, a small piece of the parent human salivary protein mucin, killed 92 percent of the fungal agent C. albicans in saliva in vitro."
Bobek presented her study findings yesterday at the International Association of Dental Research meeting in Hawaii.
Peptides are susceptible to enzyme degradation in saliva, which makes them less active or completely inactive. That is not the case with MUC7 12-mer-D, however, Bobek noted. "This peptide, in which D-amino acid derivatives are substituted for natural L-amino acids (producing a mirror images of the original), is not recognized and thus not broken down by protein-degrading enzymes in saliva," she said.
To prove this point, Bobek tested the activity of the peptide in saliva and salt solutions containing C. albicans, and compared its fungicidal activity with MUC 12-mer, natural L form, the normal configuration of the peptide. This peptide also is active against C. albicans, but it is susceptible to enzyme degradation.
Results showed that in saliva, at 100 micromolar concentration, the D peptide killed 95 percent of the organism, while the L peptide killed only 56 percent. In the salt solution, and at much lower concentration (25 micromolar), the D peptide killed 85 percent of the fungal agent, while the L form killed less than 20 percent. The D peptide also was much less toxic than current treatments.
Even at the relatively high concentration of 100 micromolar, the D peptide showed little destruction of red blood cells, a standard measure of toxicity, she noted.
Bobek next will test the antifungal activity of MUC7 12-mer-D in a mouse model of oral candidiasis.
"This peptide appears to be an excellent candidate for testing its antifungal activity in an animal model," said Bobek. "We are looking for an alternative treatment that is more natural and hopefully less toxic."
Guo-Xian Wei, postdoctoral associate in the Department of Oral Biology, is co-investigator on the study.
The research was supported by a grant from the National Institute of Dental and Craniofacial Research (NIDCR).