What is proposed is to continue and expand a collaboration between an outstanding peptide and organic synthesis laboratory in Latvia and an outstanding cytoskeleton laboratory in Boston. Potential actin or polyphosphoinositide lipid (PPI)-binding peptides will be synthesized based on the sequences of various proteins identified by genetic or biochemical data. The structures of some peptides will be calculated by molecular modeling in Riga and their biochemical effects on lipids, actin binding proteins, and intact cells will be studied in Boston. These studies will be expanded to include fluorescent peptides shown to retain the PPI-binding properties of unlabeled analogs. One of these peptides exhibits the unusual property of crossing the plasma membrane of living cells. This peptide has potential applications as a research tool to identify or disrupt PPI localization in vivo or clinically as a carrier of pharmaceutical agents into specific cell types. These possibilities will be tested using derivatives synthesized in Riga and shown in Boston to form gels at very low concentration by assembling into rodlike micelles. These peptide gels are ideal materials to be studied by rheologic methods and have potential for application in drug delivery or antigen presentation.
