Of critical importance in drug delivery and tissue engineering applications is the degradabilty of implanted polymeric materials. The use of peptide-derived crosslinkers 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 crosslinker. 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 non-chemoselective 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.

Depsipeptide analogues of auto-inducing peptides (AIPs) from all four Staphylococcus aureus subgroups were prepared as panning reagents for in vitro antibody selection. Stepwise Fmoc solid-phase synthesis was used to prepare the linear precursors, which were cyclized without epimerization in a one-pot cleavage reaction following oxidation of the stable acylphenylhydrazine linkage to the reactive acylphenyldiazene.