Polyanionic drugs and viral oncogenesis: a novel approach to control infection, tumor-associated inflammation and angiogenesis.
Polyanionic macromolecules are extremely abundant both in the extracellular environment and inside the cell, where they are readily accessible to many proteins for interactions that play a variety of biological roles. Among polyanions, heparin, heparan sulfate proteoglycans (HSPGs) and glycosphingolipids (GSLs) are widely distributed in biological fluids, at the cell membrane and inside the cell, where they are implicated in several physiological and/or pathological processes such as infectious diseases, angiogenesis and tumor growth. At a molecular level, these processes are mainly mediated by microbial proteins, cytokines and receptors that exert their functions by binding to HSPGs and/or GSLs, suggesting the possibility to use polyanionic antagonists as efficient drugs for the treatment of infectious diseases and cancer. Polysulfated (PS) or polysulfonated (PSN) compounds are a heterogeneous group of natural, semi-synthetic or synthetic molecules whose prototypes are heparin and suramin. Different structural features confer to PS/PSN compounds the capacity to bind and inhibit the biological activities of those same heparin-binding proteins implicated in infectious diseases and cancer. In this review we will discuss the state of the art and the possible future development of polyanionic drugs in the treatment of infectious diseases and cancer.
Urbinati
Chiara
C
Department of Biomedical Sciences and Biotechnology, Unit of General Pathology and Immunology, School of Medicine, University of Brescia, Italy. urbinati@med.unibs.it
Chiodelli
Paola
P
Rusnati
Marco
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000071228:Polyelectrolytes; D011108:Polymers