Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogels composed of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were prepared by redox polymerization with peptide cross-linkers to create an artificial extracellular matrix (ECM) amenable for testing hypotheses regarding cell proliferation and migration in three dimensions. Peptide degradable cross-linkers were synthesized by the acrylation of the amine groups of glutamine and lysine residues within peptide sequences potentially cleavable by matrix metalloproteinases synthesized by mammalian cells (e.g., osteoblasts). With the peptide cross-linker, loosely cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content, and enzymatic degradation properties were investigated. The peptide-cross-linked P(NIPAAm-co-AAc) hydrogels were pliable and fluidlike at room temperature and could be injected through a small-diameter aperture. The LCST of peptide-cross-linked hydrogel was influenced by the monomer ratio of NIPAAm/AAc but not by cross-linking density within the polymer network. A peptide-cross-linked hydrogel with a 97/3 molar ratio of NIPAAm/AAc exhibited a LCST of approximately 34.5 degrees C. Swelling was influenced by NIPAAm/AAc monomer ratio, cross-linking density, and swelling media; however, all hydrogels maintained more than 90% water even at 37 degrees C. In enzymatic degradation studies, breakdown of the peptide-cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on both the concentration of collagenase and the cross-linking density. These results suggest that peptide-cross-linked P(NIPAAm-co-AAc) hydrogels can be tailored to create environmentally-responsive artificial extracellular matrixes that are degraded by proteases.
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PMID:Synthesis and characterization of injectable poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with proteolytically degradable cross-links. 1295 86

Novel thermoreversible copolymers of N-isopropylacrylamide (NIPAAm) with collagenase-sensitive solubility behavior were synthesized by radical polymerization of poly(NIPAAm-co-NASI) and nucleophilic substitution of custom peptides GAPGL-NH(2) and GAPGLF-NH(2). The materials were characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography in conjunction with static light scattering, differential scanning calorimetry (DSC), and cloud point determination. Successful synthesis and specific degradation by collagenase above and below the material LCST was confirmed by NMR. The LCST behavior of the polymers was affected by collagenase. The LCST of the copolymers, as measured by cloud point determination, increased by 1 and 9 degrees C, respectively, after enzymatic degradation. DSC thermographs indicated increased polymer solubility after enzymatic degradation because of a reduced energy of gelation. These results demonstrate the significant impact of a single amino acid on the LCST behavior of thermosensitive copolymers. Furthermore, the results suggest that comonomers in similar systems could be designed to elicit phase transitions or conformation changes in response to a variety of enzymes for which the substrate structure is known.
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PMID:Bioresponsive copolymers of poly(N-isopropylacrylamide) with enzyme-dependent lower critical solution temperatures. 2038 Mar 71

Many biological processes require precise regulation and synergy of proteins, and consequently involve molecular recognition and spatial constraints between biomolecules. Here, a library of poly(N-isopropylacrylamide-co-tris-nitrilotriacetic acid acrylamide) (PNTs) has been synthesized and complexed with Cu(2+) in order to serve as models for investigation of the combined effects of molecular recognition and spatial constraints in biomolecular interactions. The average distance between Cu(2+)-trisNTA binding sites in PNTs polymers was varied from 4.3 to 31.5 nm by adjusting their trisNTA contents. His tag (His6), His-tagged enhanced yellow fluorescent protein (His6-eYFP), and His6-tagged collagenase G (His6-ColG), with sizes ranging from 1 to 11 nm, were used as models to assess whether the binding ability is influenced by a cooperative topology based on molecular recognition interactions with Cu(2+)-trisNTA binding sites, and spatial constraints created by decreasing average distance between trisNTAs. His-tagged molecules bound to all PNTs polymers due to their molecular recognition interaction involving histidines and Cu(2+)-trisNTA pockets, but with a binding ability that was highly modulated by the average distance between the trisNTA binding sites. Small molecular mass molecules (His6) exhibit a high binding ability to all PNTs polymers, whereas his-tagged proteins bind to PNTs efficiently only when the average distance between trisNTA binding sites is larger than the protein dimensions.
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PMID:Poly(N-isopropylacrylamide-co-tris-nitrilotriacetic acid acrylamide) for a combined study of molecular recognition and spatial constraints in protein binding and interactions. 2514 32

In this study, we present gelatin-based thermoresponsive colloidal microgels that enable the controlled release of drugs by volume phase transition. The microgel was fabricated by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within three-dimensional gelatin networks crosslinked by genipin. We demonstrate that our gelatin-based thermoresponsive microgel exhibits a tunable deswelling to temperature increase, which positively correlated to the release of bovine serum albumin (BSA) as a function of poly(N-isopropylacrylamide-co-acrylamide) concentration. The microgel was enzymatically degradable by collagenase treatment. The extent of BSA release and biodegradability were tuned by controlling the crosslinking degree of the gelatin matrix. Meeting a great need for design and synthesis of auto-degenerating smart microgels that enable the controlled release of therapeutic proteins in responsive to external stimuli, our gelatin-based microgels that satisfy both thermoresponsivity and biodegradability have a great potential in tissue engineering applications as a soft microdevice element for drug delivery.
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PMID:Biodegradable colloidal microgels with tunable thermosensitive volume phase transitions for controllable drug delivery. 2579 95

External triggers such as pH or temperature can induce hydrogels to swell or shrink rapidly. Recently, these triggers have also been used to alter the three-dimensional (3-D) shapes of gels: for example, a flat gel sheet can be induced to fold into a tube. Self-folding gels are reminiscent of natural structures such as the Venus flytrap, which folds its leaves to entrap its prey. They are also of interest for applications in sensing or microrobotics. However, to advance the utility of self-folding gels, the range of triggers needs to be expanded beyond the conventional ones. Toward this end, we have designed a class of gels that change shape in response to very low concentrations of specific biomolecules. The gels are hybrids of three different constituents: (A) polyethylene glycol diacrylate (PEGDA); (B) gelatin methacrylate-co-polyethylene glycol dimethacrylate (GelMA-co-PEGDMA); and (C) N-isopropylacrylamide (NIPA). The thin-film hybrid is constructed as a bilayer or sandwich of two layers, with an A/B layer (alternating strips of A and B) sandwiched above a layer of gel C. Initially, when this hybrid gel is placed in water, the C layer is much more swollen than the A/B layer. Despite the swelling mismatch, the sheet remains flat because the A/B layer is very stiff. When collagenase enzyme is added to the water, it cleaves the gelatin chains in B, thus reducing the stiffness of the A/B layer. As a result, the swollen C layer is able to fold over the A/B layer, causing the sheet to transform into a specific shape. The typical transition is from flat sheet to closed hollow tube, and the time scale for this transition decreases with increasing enzyme concentration. Shape transitions are induced by enzyme levels as low as 0.75 U/mL. Interestingly, a shape transition is also induced by adding the lysate of murine fibroblast cells, which contains enzymes from the matrix metalloproteinase (MMP) family at levels around 0.1 U/mL (MMPs are similar to collagenase in their ability to cleave gelatin). We further show that transitions from flat sheets to other shapes such as helices and pancakes can be engineered by altering the design pattern of the gel. Additionally, we have made a rudimentary analog of the Venus flytrap, with two flat gels ("leaves") flanking a central folding gel ("hinge"). When enzyme is added, the hinge bends and brings the leaves together, trapping objects in the middle.
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PMID:Enzyme-Triggered Folding of Hydrogels: Toward a Mimic of the Venus Flytrap. 2740 25