Increasing cytostatic effects of ricin A chain and Staphylococcus aureus enterotoxin A through in vitro hydrophobization with fatty acid residues.
In order to impart an ability for receptor-independent transmembrane transfer to water-soluble proteins, it has been suggested that they be hydrophobized by lipid groups (fatty acids, etc.). To this end, systems of reversed micelles of surfactants in organic solvents were used as reaction media for protein modification. It was shown that after introduction of a hydrophobic anchor (stearic acid residue) the toxic effect of ricin A-chain (in the absence of B-chain) on intact cells became very close to that of the native toxin. As a result of stearic acid acylation, the activity of Staphylococcal enterotoxin A increased by nearly 1.5-2 orders. The observed phenomena can be explained by receptor-independent intracellular translocation of the hydrophobized toxins.
Alakhov VYu
Research Center of Molecular Diagnostics, USSR Ministry of Health, Moscow.
Kabanov
A V
AV
Batrakova
E V
EV
Koromyslova
I A
IA
Levashov
A V
AV
Severin
E S
ES
D000215:Acylation; D002460:Cell Line; D002470:Cell Survival; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000096:biosynthesis*; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008823:Micelles; D012276:Ricin / Q000494:pharmacology*; D013229:Stearic Acids; D013329:Structure-Activity Relationship
D004768:Enterotoxins; D008823:Micelles; D013229:Stearic Acids; C026066:enterotoxin A, Staphylococcal; C031183:stearic acid; D004247:DNA; D012276:Ricin