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Chem Rev. 2018 Sep 26;118(18):9152-9232. doi: 10.1021/acs.chemrev.8b00354. Epub 2018 Sep 11.

Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics.

Author information

1
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry , University of Patras , Patras 26110 , Greece.
2
Foundation for Research and Technology-Hellas (FORTH) / Institute of Chemical Engineering Sciences (ICE-HT) , Patras 26110 , Greece.
3
Institute for Molecular Science of Medicine , Aichi Medical University , Aichi 480-1195 , Japan.
4
Department for Life Quality Studies , University of Bologna , Rimini 47100 , Italy.
5
Université de Reims Champagne-Ardenne, Laboratoire SiRMa, CNRS UMR MEDyC 7369 , Faculté de Médecine , 51 rue Cognacq Jay , Reims 51100 , France.
6
Université de Reims Champagne-Ardenne, Laboratoire de Biochimie Médicale et Biologie Moléculaire, CNRS UMR MEDyC 7369 , Faculté de Médecine , 51 rue Cognacq Jay , Reims 51100 , France.
7
Department of Gynecology and Obstetrics , Münster University Hospital , Münster 48149 , Germany.
8
Department of Medicine and Surgery , University of Insubria , Varese 21100 , Italy.
9
University Claude Bernard Lyon 1 , CNRS, UMR 5246, Institute of Molecular and Supramolecular Chemistry and Biochemistry , Villeurbanne 69622 , France.
10
Department of Pathology, Comprehensive Cancer Center , University of Alabama at Birmingham , Birmingham , Alabama 35294 , United States.
11
Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College , Thomas Jefferson University , Philadelphia , Pennsylvania 10107 , United States.

Abstract

The extracellular matrix (ECM) constitutes a highly dynamic three-dimensional structural network comprised of macromolecules, such as proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, fibronectin, elastin, other glycoproteins and proteinases. In recent years, the field of PGs has expanded rapidly. Due to their high structural complexity and heterogeneity, PGs mediate several homeostatic and pathological processes. PGs consist of a protein core and one or more covalently attached GAG chains, which provide the protein cores with the ability to interact with several proteins. The GAG building blocks of PGs significantly influence the chemical and functional properties of PGs. The primary goal of this comprehensive review is to summarize major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry-biology axis, focusing on structural variability, structure-function relationships, metabolic, molecular, and epigenetic mechanisms underlying their synthesis. Recent insights related to exosome biogenesis, degradation, and cell signaling, their status as diagnostic tools and potential pharmacological targets in diseases as well as current applications in nanotechnology and biotechnology are addressed. Moreover, issues related to docking studies, molecular modeling, GAG/PG interaction networks, and their integration are discussed.

PMID:
30204432
DOI:
10.1021/acs.chemrev.8b00354
[Indexed for MEDLINE]

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