MFAME, N-methyl-N-d-fructosyl amphotericin B methyl ester, a new amphotericin B derivative of low toxicity: relationship between self-association and effects on red blood cells

Szlinder-Richert, Joanna; Mazerski, Jan; Cybulska, Barbara; Grzybowska, Jolanta; Borowski, Edward

doi:10.1016/s0304-4165(01)00166-0

Cited by 53 publications

(45 citation statements)

References 20 publications

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“…The high therapeutic value of AmB is associated with its advantageous biological properties such as broad antimicrobial spectrum, high fungicidal activity, reluctance to induce a secondary resistance, and activity against multidrug-resistant strains [3,4]. Owing to these properties AmB can be considered as a promising lead compound for the development of novel antifungal drugs [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Neumann

Borowski

Bagiński

2009

Biophysical Chemistry

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. Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives -a molecular dynamics study. Biophysical Chemistry, Elsevier, 2009, 141 (1) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Author to whom the correspondence should be addressed. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 AbstractAmphotericin B (AmB) is an effective but very toxic antifungal antibiotic. In our laboratory a series of AmB derivatives of improved selectivity of action was synthesized and tested. To understand molecular basis of this improvement, comparative conformational studies of amphotericin B and its two more selective derivatives were carried out in an aqueous solution and in a lipid membrane. These molecular simulation studies revealed that within a membrane environment the conformational behavior of the derivatives differs significantly from the one observed for the parent molecule. Possible reasons for such a difference are analyzed. Furthermore, we hypothesize that the observed conformational transition within the polar head of AmB derivatives may lead to destabilization of antibioticinduced transmembrane channels. Consequently, the selective toxicity of the derivatives should increase as ergosterol-rich liquid-ordered domains are more rigid and conformationally ordered than their cholesterol-containing counterparts, and as such may better support less stable channel structure.

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Section: Introductionmentioning

confidence: 99%

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Neumann

Borowski

Bagiński

2009

Biophysical Chemistry

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“…Another problem with amphotericin B is its tendency to aggregate in aqueous solution, which further diminishes its selective toxicity. Monomers show antifungal specificity whereas aggregates are equally damaging towards fungal and mammalian cells (Szlinder-Richert et al, 2001). Liposomal amphotericins show reduced toxicity, possibly because they release monomers slowly (Lemke et al, 2005).…”

Section: Production Of Polyene Analogues By Chemical and Biological Mmentioning

confidence: 99%

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

Caffrey

Poire

Sheehan

et al. 2016

Appl Microbiol Biotechnol

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“…Chemical modification studies have shown that this increases watersolubility and reduces toxicity. 11,12) Alteration of GT substrate specificity requires replacement of key amino acid residues or domain swapping. 13,14) The task is challenging and requires systems for testing large numbers of recombinant transferases for novel activities.…”

Section: )mentioning

confidence: 99%

Streptomyces nodosusHost Strains Optimized for Polyene Glycosylation Engineering

Stephens¹,

Rawlings²,

Caffrey³

2012

Bioscience, Biotechnology, and Biochemistry

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MFAME, N-methyl-N-d-fructosyl amphotericin B methyl ester, a new amphotericin B derivative of low toxicity: relationship between self-association and effects on red blood cells

Cited by 53 publications

References 20 publications

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

Streptomyces nodosusHost Strains Optimized for Polyene Glycosylation Engineering

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