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A Biomimetic of Endogenous Tissue Inhibitors of Metalloproteinases: Inhibition Mechanism and Contribution of Composition, Polymer Size, and Shape to the Inhibitory Effect
- Source :
- Nano Letters. 21:5663-5670
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- A biomimetic of endogenous tissue inhibitors of metalloproteinases (TIMPs) was engineered by introducing three binding elements to a synthetic tetrapolymer. We evaluated the contribution of composition, size, and shape of the TIMP-mimicking polymers to the inhibition of BaP1, a P-I class snake venom metalloproteinase (SVMP). Inhibition was achieved when the size of the linear polymer (LP) was comparable to or greater than that of the enzyme, indicating the efficacy requires binding to a significant portion of the enzyme surface in the vicinity of the active site. The efficacy of a low cross-linked polymer hydrogel nanoparticle (NP) of substantially greater molecular weight was comparable to that of the LPs despite differences in size and shape, an important finding for in vivo applications. The abiotic TIMP was effective against two classes of SVMPs in whole snake venom. The results can serve as a design principle for biomimetic polymer inhibitors of enzymes.
- Subjects :
- Polymers
Bioengineering
Endogeny
02 engineering and technology
Matrix metalloproteinase
Biomimetics
In vivo
Catalytic Domain
General Materials Science
chemistry.chemical_classification
Metalloproteinase
biology
Mechanical Engineering
Active site
Tissue Inhibitor of Metalloproteinases
General Chemistry
Polymer
021001 nanoscience & nanotechnology
Condensed Matter Physics
Enzyme
chemistry
Snake venom
biology.protein
Biophysics
0210 nano-technology
Snake Venoms
Subjects
Details
- ISSN :
- 15306992 and 15306984
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Nano Letters
- Accession number :
- edsair.doi.dedup.....9651b3ddda9f85e34f0ced62c45399be