Rationally designed peptides for controlled release of nerve growth factor from fibrin matrices.
The purpose of this research was to identify peptide sequences with varying affinity for nerve growth factor (NGF) and use them in the rational design of affinity-based drug delivery systems. A phage display library (12 amino acid random peptide sequence) was screened against NGF-conjugated chromatography resin three times and fractions containing phage of varying affinity were eluted by decreasing the pH of the eluent. These phages were isolated, amplified; then their DNA was purified and sequenced to determine the identity of the random peptide domain. Consensus peptides based on these sequences were synthesized and screened for their ability to bind NGF and release it at different rates from fibrin matrices. The ability of fibrin matrices containing these peptides and NGF to deliver to biologically active NGF was tested using a chick dorsal root ganglia model. A mathematical model was developed to further understand how the affinity of a peptide can modulate release of NGF and to aid in design optimization for the delivery system. The peptides identified in this study were determined to have varying affinities for NGF suggesting that this approach can serve as a model for tailoring the affinity of a drug delivery system for a target protein drug.
Willerth
Stephanie M
SM
Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA.
Johnson
Philip J
PJ
Maxwell
Dustin J
DJ
Parsons
Sarah R
SR
Doukas
Maria E
ME
Sakiyama-Elbert
Shelly E
SE
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry*; D008956:Models, Chemical; D020932:Nerve Growth Factor / Q000737:chemistry* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding
D003692:Delayed-Action Preparations; D019151:Peptide Library; D010455:Peptides; D005337:Fibrin; D020932:Nerve Growth Factor