Leishmania mexicana: chemistry and biochemistry of sodium stibogluconate (Pentostam).
The chemical properties of the primary antileishmanial agent sodium stibogluconate (Pentostam), and the interaction of Pentostam with Leishmania mexicana amastigotes, have been investigated with the aid of [125Sb]Pentostam. The molecular weight by P2 chromatography showed [125Sb]Pentostam to be of multiple species of MW = 100-4000 Da, rather than the one species of 746 Da predicted by the commonly hypothesized structural formula. Nonradioactive Pentostam had a lower osmolarity (789 mOsm for a 100 mg Sb/ml solution) than predicted (1644 mOsm), which indicates that the multiple components of Pentostam (Sb and derivatives of gluconic acid) are more closely complexed with each other than previously thought. When incubated with L. mexicana amastigotes, labeled drug was bound to at least six polypeptides of molecular weights ranging from 14,000 to 68,000 Da as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Interaction with the polypeptides is presumed to contribute to the antileishmanial action of Pentostam.
Berman
J D
JD
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C. 20307-5100.
Grogl
M
M
D000042:Absorption; D000818:Animals; D000965:Antimony; D000967:Antimony Sodium Gluconate / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D004247:DNA / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D019286:Endopeptidase K; D005942:Gluconates / Q000494:pharmacology*; D007894:Leishmania mexicana / Q000032:analysis / Q000187:drug effects*; D008970:Molecular Weight; D009994:Osmolar Concentration; D010455:Peptides / Q000032:analysis; D011868:Radioisotopes; D012697:Serine Endopeptidases; D013053:Spectrophotometry
D005942:Gluconates; D010455:Peptides; D011868:Radioisotopes; D004247:DNA; D000965:Antimony; D012697:Serine Endopeptidases; D019286:Endopeptidase K; D000967:Antimony Sodium Gluconate