Sodium hyaluronate-g-2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide with enhanced affinity towards MMP12 catalytic domain to be used as visco-supplement with increased degradation resistance

Gemma Leone; Simone Pepi; Marco Consumi; Stefania Lamponi; Marco Fragai; Marco Martinucci; Veronica Baldoneschi; Oscar Francesconi; Cristina Nativi; Agnese Magnani

doi:10.1016/j.carbpol.2021.118452

Sodium hyaluronate-g-2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide with enhanced affinity towards MMP12 catalytic domain to be used as visco-supplement with increased degradation resistance

Carbohydr Polym. 2021 Nov 1:271:118452. doi: 10.1016/j.carbpol.2021.118452. Epub 2021 Jul 16.

Authors

Affiliations

¹ Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy; National Interuniversity Consortium of Materials Science and Technology (INSTM), Via Giusti 9, 50121 Firenze, Italy.
² Department of Chemistry, "Ugo Schiff" - University of Florence - Via della Lastruccia 13, 50019 Sesto Fiorentino, FI, Italy; Cerm, University of Florence, via L. Sacconi 6, 50019 Sesto Fiorentino, FI, Italy.
³ Department of Chemistry, "Ugo Schiff" - University of Florence - Via della Lastruccia 13, 50019 Sesto Fiorentino, FI, Italy.
⁴ Department of Chemistry, "Ugo Schiff" - University of Florence - Via della Lastruccia 13, 50019 Sesto Fiorentino, FI, Italy; National Interuniversity Consortium of Materials Science and Technology (INSTM), Via Giusti 9, 50121 Firenze, Italy.
⁵ Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy; National Interuniversity Consortium of Materials Science and Technology (INSTM), Via Giusti 9, 50121 Firenze, Italy. Electronic address: agnese.magnani@unisi.it.

PMID: 34364546
DOI: 10.1016/j.carbpol.2021.118452

Abstract

The present paper describes the functionalization of sodium hyaluronate (NaHA) with a small molecule (2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide) (MMPI) having proven inhibitory activity against membrane metalloproteins involved in inflammatory processes (i.e. MMP12). The obtained derivative (HA-MMPI) demonstrated an increased resistance to the in-vitro degradation by hyaluronidase, viscoelastic properties close to those of healthy human synovial fluid, cytocompatibility towards human chondrocytes and nanomolar affinity towards MMP 12. Thus, HA-MMPI can be considered a good candidate as viscosupplement in the treatment of knee osteoarticular disease.

Keywords: Degradation; Hyaluronic acid; MMP inhibitors; Synovial fluid; Viscosupplementation.

MeSH terms

Catalytic Domain
Chondrocytes / drug effects
Hyaluronic Acid / chemical synthesis
Hyaluronic Acid / metabolism
Hyaluronic Acid / pharmacology*
Hyaluronic Acid / toxicity
Hydroxamic Acids / chemical synthesis
Hydroxamic Acids / metabolism
Hydroxamic Acids / pharmacology*
Hydroxamic Acids / toxicity
Matrix Metalloproteinase 12 / chemistry
Matrix Metalloproteinase 12 / metabolism
Matrix Metalloproteinase Inhibitors / chemical synthesis
Matrix Metalloproteinase Inhibitors / metabolism
Matrix Metalloproteinase Inhibitors / pharmacology*
Matrix Metalloproteinase Inhibitors / toxicity
Protein Binding
Sulfonamides / chemical synthesis
Sulfonamides / metabolism
Sulfonamides / pharmacology*
Sulfonamides / toxicity
Viscoelastic Substances / chemical synthesis
Viscoelastic Substances / metabolism
Viscoelastic Substances / pharmacology*
Viscoelastic Substances / toxicity

Substances

Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Sulfonamides
Viscoelastic Substances
Hyaluronic Acid
Matrix Metalloproteinase 12