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Lipid modification of proteins and their membrane transport
Authors:Kabanov  Alexander V; Levashov  Andrey V; Alakhov  Valery Yu
Affiliation:Division for Chemical Enzymology, Chemical Department, Moscow State University Moscow 119899 1Research Centre of Molecular Diagnostics, USSR Ministry of Health Moscow 113149, USSR
Abstract:An effective method for artificial attachment of lipid anchorsto water-soluble proteins has been developed. To this end, aprotein molecule is modified in a system of reversed micellesby a water-insoluble reagent, e.g. fatty acid chloride. Fattyacylated proteins acquire an ability to translocate across lipidmembranes and penetrate intact cells. This principle of impartingtransmembrane properties to water-soluble proteins makes itpossible to realize in vivo a direct transport of antibodiesacross the hemato-encephalic barrier into the brain and to developa method for virus suppression by fatty acylated anti-viralantibodies capable of penetrating infected cells. The effectof a drastic increase in the biological activity of exogenousprotein factors, e.g. Staphylococcus aureus enterotoxin A, asa result of their artificial fatty acylation has been discovered.The above-mentioned phenomena are discussed in relation to thein vivo data, indicating that post-translational modificationof proteins by fatty acids and phospholipids is very widespreadin nature and evidently plays an important role in protein transportand sorting. In this connection, lipid modification of proteinsis regarded as a possible general step of protein transportin vivo.
Keywords:biomembranes/  drug transport/  lipid anchors/  protein translocation/  toxins
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