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Biosynthesis of amphotericin derivatives lacking exocyclic carboxyl groups
Alternative Title
Biosynthesis of less toxic amphotericins
Date Issued
2005-08-03
Date Available
2019-04-18T09:23:31Z
Abstract
Amphotericin B is a medically important antifungal antibiotic that is also active against human immunodeficiency virus, Leishmania parasites, and prion diseases. The therapeutic use of amphotericin B is restricted by severe side effects that can be moderated by liposomal formulation or structural alteration. Chemical modification has shown that suppression of charge on the exocyclic carboxyl group of amphotericin B substantially reduces toxicity. We report targeted deletions of the amphN cytochrome P450 gene from the chromosome of the amphotericin-producing bacterium Streptomyces nodosus. The mutant strains produced amphotericin analogues in which methyl groups replace the exocyclic carboxyl groups. These compounds retained antifungal activity and had reduced hemolytic activity.
Sponsorship
Higher Education Authority
Other Sponsorship
European Union
Type of Material
Journal Article
Publisher
ASBMB
Journal
Journal of Biological Chemistry
Volume
280
Issue
41
Start Page
34420
End Page
34426
Copyright (Published Version)
2005 The American Society for Biochemistry and Molecular Biology
Web versions
Language
English
Status of Item
Peer reviewed
ISSN
0021-9258
This item is made available under a Creative Commons License
File(s)
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Name
Caffrey JBC paper 2005.pdf
Size
423.68 KB
Format
Adobe PDF
Checksum (MD5)
49ba21620bea6cbc86549e61baf5863c
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