Controlled release of phosphorothioates by protein-based polymers.
Protein-based polymers are water soluble at lower temperatures but undergo a phase transition with increasing temperature. The polymers' hydrophobicity controls the transition temperature and the free energy of its charged groups through an apolar-polar repulsive free energy of hydration, which drives the binding of charged drugs. Binding and release of phosphorothioates were obtained with polymers containing 1 lysine alone or coupled with 2 to 5 phenylalanines per 30 residues. Release rates from 4 to 64 nmol/ cm2/day were maintained constant for 8 to 2 weeks/mm, respectively. We demonstrated the ability of protein-based polymers to deliver nucleic acid based therapeutics with high programmability.
Woods
T Cooper
TC
Bioelastics, Inc., Vestavia Hills, Alabama, USA.
Urry
Dan W
DW
D003692:Delayed-Action Preparations; D008239:Lysine / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D044366:Transition Temperature
D003692:Delayed-Action Preparations; D016376:Oligonucleotides, Antisense; D010710:Phosphates; D011108:Polymers; D011994:Recombinant Proteins; D010649:Phenylalanine; C083120:phosphorodithioic acid; D008239:Lysine