amyloid as a depot for the formulation of long-acting drugs淀粉样蛋白作为长效药物的配方的仓库.pdfVIP

PLoS BIOLOGY Amyloid as a Depot for the Formulation of Long-Acting Drugs 1 2 3 3 3 1,4* Samir K. Maji , David Schubert , Catherine Rivier , Soon Lee , Jean E. Rivier , Roland Riek 1 Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America, 2 Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America, 3 The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, California, United States of America, 4 Laboratory for Physical Chemistry, Zurich, Switzerland Amyloids are highly organized protein aggregates that are associated with both neurodegenerative diseases such as Alzheimer disease and benign functions like skin pigmentation. Amyloids self-polymerize in a nucleation-dependent manner by recruiting their soluble protein/peptide counterpart and are stable against harsh physical, chemical, and biochemical conditions. These extraordinary properties make amyloids attractive for applications in nanotechnology. Here, we suggest the use of amyloids in the formulation of long-acting drugs. It is our rationale that amyloids have the properties required of a long-acting drug because they are stable depots that guarantee a controlled release of the active peptide drug from the amyloid termini. This concept is tested with a family of short- and long-acting analogs of gonadotropin-releasing hormone (GnRH), and it is shown that amyloids thereof can act as a source for the sustained release of biologically active peptides. Citation: Maji SK, Schubert D, Rivier C, Lee S, Rivier JE, et al. (2008) Amyloid as a depot for the formulation of long-acting drugs. PLoS Biol 6(2): e17. doi:10.1371/journal.pbio. 0060017 Introduction