Solid-phase synthesis and kinetic characterization of fluorogenic enzyme-degradable hydrogel cross-linkers.
Of critical importance in drug delivery and tissue engineering applications is the degradability of implanted polymeric materials. The use of peptide-derived cross-linkers in hydrogel design is a valuable approach by which polymeric carriers can be endowed with enzymatic degradability in a predictable, "programmable" fashion. The solid-phase synthesis strategy described herein allows for an expeditious, flexible synthesis of bis-acrylamide-derivatized peptides with complex modifications, as exemplified by the incorporation of fluorophore and quencher moieties into a matrix metalloprotease (MMP)-degradable cross-linker. The crude synthetic product was obtained in high yield and purity and purified by standard methods; it was then used directly for polymerization without the need for tedious and often nonchemoselective solution-phase modifications. Functional appendages incorporated for detection provided a direct, quantitative link between enzymatic activity and hydrogel degradation using routine methods for identification of optimal enzyme-specific degradability.
Moss
Jason A
JA
Department of Chemistry, The Skaggs Institute of Chemical Biology, and Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Stokols
Shula
S
Hixon
Mark S
MS
Ashley
Fawn T
FT
Chang
Jason Y
JY
Janda
Kim D
KD
D000178:Acrylamides / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D020782:Matrix Metalloproteinases / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry
D000178:Acrylamides; D010455:Peptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020782:Matrix Metalloproteinases