PubMed HealthSearch

Biomedical subjects

A R Balakrishnan

Publications and source records attributed to A R Balakrishnan.

5 recordsLinked to original sources

CD and NMR studies on the aggregation of amphotericin-B in solution.

We report in this paper the aggregation properties of amphotericin-B (amp-B) in solution using CD and 1H-NMR techniques. Our results indicate that the preferred structure of amp-B in dimethylsulfoxide is a monomer at low concentrations (10(-4) M and below) and a stable dimer at higher concentrations (range 5.10(-3) M to 10(-2) M). In a DMSO/ethanol mixture (1:1 (v/v)), the antibiotic is monomeric, irrespective of the concentration within the range studied. We propose a head-to-tail model based on NMR data. An understanding of the head-to-tail dimer, is, we believe important, particularly in view of the recent report wherein it is proposed that the drug inserts into bilayers as head-to-tail oligomers.

Amphotericin B

Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes.

The interactions between the polyene antibiotic amphotericin B with dipalmitoylphosphatidylcholine were investigated in vesicles (using circular dichroism) and in chloroform solution (using circular dichroism and 1H, 13C, and 31P nuclear magnetic resonance). The results show that amphotericin B readily aggregates in vesicles and that the extent of aggregation depends on the lipid:drug concentration ratio. Introduction of sterol molecules into the membrane hastens the process of aggregation of amphotericin B. In chloroform solutions amphotericin B strongly interacts with phospholipid molecules to form a stoichiometric complex. The results suggest that there are interactions between the conjugated heptene stretch of amphotericin B and the methylene groups of lipid acyl chains, while the sugar moiety interacts with the phosphate head group by the formation of a hydrogen bond. A model is proposed for the lipid-amphotericin B complex, in which amphotericin B interacts equally well with the two lipid acyl chains, forming a 1:1 complex.

1,2-Dipalmitoylphosphatidylcholine

Conformation of polyene antibiotic, filipin III: CD and 1H NMR studies.

Detailed studies on the solution conformation of polyene antibiotic, filipin III using circular dichroism (CD) and proton nuclear magnetic resonance techniques have been carried out. In dimethyl sulfoxide (DMSO), filipin III exhibits concentration dependent aggregation-monomeric at lower and oligomeric at higher concentrations of the antibiotic. At concentrations used for 1H NMR studies (6 x 10(-3)M) the molecule coexists as monomeric and oligomeric species. However, titration experiments indicated that, in a mixed solvent system of DMSO:methanol (2:3 v/v) the antibiotic exists only as a monomer. Complete 1H NMR assignments and the conformation of the monomer filipin III have been determined by the combined use of DQFCOSY and ROESY experiments in DMSO:methanol solvent system.

Circular Dichroism