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ID 19888
本文ファイル
著者
Fukashima, H.
Makihira, Seicho
Hamada, Taizo
Samaranayake, L.P.
キーワード
cationic peptide
antifungal activity
Candida albicans
NDC
医学
抄録(英)
OBJECTIVE: Peptide antibiotics are considered a new class of antifungal agents. Of these, an α-helical, cationic peptide termed Dhvar 4, a relative of salivary histatin has been shown to be an antifungal of relatively high potency. Similarly, lactoferricin B (LFB) and a derivative thereof, LFB(17-30), disrupts the fungal cell membrane and acts against Candida albicans. As Dhvar 4 and LFB(17-30), exhibit almost identical amino acid sequences at their C-terminal, we hypothesized that laboratory synthesis of peptides with an α-helical structure and having similar amphipathic properties could lead to products with candidacidal activity. Hence, three such peptides - JH8194, JH8195 and JH 8944, were synthesized and their antifungal properties compared with recognized antifungals LFB, LFB(17-30), human lactoferricin (LFH), Histatin-5 and Dhvar 4, against two isolates of C. albicans.

MATERIALS AND METHODS: The antifungal agents were synthesized and their secondary structures evaluated according to a previously described protocol of Situ and Bobek (2000) Antimicrob Agents Chemother 44: 1485-1493. The C. albicans strains were oral isolates from a human immunodeficiency virus-infected (isolate A2) and a healthy (A6) individual. A standard concentration of yeasts was exposed to a range of dilutions of the agents for a specific duration and the cell death (viability) in terms of the resultant colony forming units ml-1 was quantified.

RESULTS: Dhvar 4, showed the most α-helical propensity, and was the least fungicidal while LFB and LFB(17-30) showed the highest antifungal potential, and demonstrated total kill of A6, and A2 at 5 and 10 μM concentrations, respectively whilst LFH killed both isolates at a 10 μM concentration. Of the three new synthetic peptides, JH 8194 was the most potent (total kill of A6/A2 strains at 1.25/2.5 μM), followed by JH 8195 (total kill of A6/A2 strains at 5/10 μM while JH 8944 was the least potent as a 25 μM concentration was required to kill either strain of Candida. On further analyses of the relationship between pl value of the peptides and their anticandicidal activity, a significant positive correlation was noted. In order to rule out a cytotoxic effect of the new synthetic peptides we compared the fungicidal and hemolytic activities under similar incubation conditions using freshly isolated erythrocytes and all three peptides exhibited no detectable hemolysis upto an concentration of 100 μM in contrast to the polyene antifungal amphotericin B that elicited significant initiation of hemolysis at a concentration of 5.0 μM.

CONCLUSION: Our data suggest that laboratory synthesis of agents with an α-helical structure and having amphipathic properties similar to known, natural antifungal agents may be a promising avenue to generate products with improved antifungal activity.
掲載誌名
Oral Diseases
10巻
4号
開始ページ
221
終了ページ
228
出版年月日
2004-07
出版者
Blackwell
ISSN
1354-523X
NCID
出版者DOI
PubMedID
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2004 Blackwell Munksgaard.
The difinitive version is available at www.blackwell-synergy.com
関連情報URL(IsVersionOf)
http://dx.doi.org/10.1111/j.1601-0825.2004.01010.x
部局名
医歯薬学総合研究科