LOLIGOMERS - DESIGN OF DE-NOVO PEPTIDE-BASED INTRACELLULAR VEHICLES

Defined branched peptides (loligomers) incorporating cytoplasmic trans location signals, nuclear localization sequences, and fluorescent prob es were designed and synthesized to demonstrate the feasibility and si mplicity of creating novel classes of intracellular vehicles: Loligome rs containing all the above signals were rapidly internalized by Chine se hamster ovary (CHO) cells and accumulated in their nucleus, At 4 de grees C, the interaction of peptide constructs with CHO cells was limi ted to membrane association. Loligomers entered cells at higher temper atures by adsorptive endocytosis, Inhibitors of ATP synthesis affected cytoplasmic import only weakly but abolished nuclear uptake, The pept ide signals guided both cytoplasmic and nuclear localization events, T he properties exhibited by loligomers suggest a strategy fdr the facil e design of ''guided'' classes of intracellular agents.