Fatty acylation of proteins for translocation across cell membranes

An effective method for the artificial attachment of lipid anchors to water-soluble proteins has been developed. Protein molecules are modified by a water-insoluble reagent, e.g. fatty acid chloride, in a reversed-micelle system. The resulting fatty acylated proteins are able to translocate across lipid membranes and penetrate intact cells. This makes possible the transport of modified antiviral antibodies across the haemato-encephalic barrier into the brain and hence virus suppression in infected cells. The effect is illustrated by the marked (hundredfold) increase in biological activity of Staphylococcus aureus enterotoxin A after fatty acylation. These phenomena are discussed in relation to in vivo data indicating that the posttranslational modification of proteins by fatty acids and phospholipids is very common in nature, and that the lipid modification of proteins may be a step in protein transport in vivo.