ABSTRACT
Self-assembling nanoparticles comprising cationic polymers are of interest for the delivery of oligonucleotide-based therapeutics. Unfortunately, exposure of the nanoparticle cationic surface to plasma and plasma proteins compromises particle stability and circulating half-life. Herein, we report that improved nanoparticle stability can be achieved through temporary grafting of PEG to the nanoparticle surface. Grafting is induced through zinc complexation between PEG-IDA and the exposed polyhistidylated polylysine (H-K) cationic polymer of pre-formed nanoparticles.
Subject(s)
Imino Acids/chemistry , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , RNA, Small Interfering/administration & dosage , Zinc/chemistry , Nanoparticles/ultrastructure , Polylysine/chemistryABSTRACT
A simple synthesis of oligoesters from TBDMS-protected-beta- and THP-protected-omega-hydroxycarboxylic acids using a solid-phase synthesis protocol is reported. Procedures were optimized for the efficient production of ion channel candidates in high purity with minimal purification. The product oligoesters were evaluated for ion transport activity using a fluorescent dye/vesicle assay. Oligoesters produced by this strategy show structure-dependent activity; the most active compounds are closely comparable to previously known oligoesters, but are available at a fraction of the synthetic effort.
Subject(s)
Combinatorial Chemistry Techniques , Esters/chemistry , Esters/chemical synthesis , Fluorescent Dyes/chemistry , Unilamellar Liposomes/chemistry , Ion Exchange , Molecular Structure , Spectrometry, FluorescenceABSTRACT
The synthesis of macrocyclic tetraesters from 5-substituted isophthalic acids and 1,8-octane diol gave macrocylic metacyclophanes with the axially symmetric positions differentially protected. Dimer bis(metacyclophane)bolaamphiphiles proved to be extremely insoluble, but one derivative was shown to have significant membrane activity. Very high continuous conductance and the formation of discrete single-ion channels were both observed, depending on how the compound was incorporated into the bilayer membrane.