Nucleic acid aptamers based on the G-quadruplex structure: therapeutic and diagnostic potential.
Aptamers are short DNA- or RNA-based oligonucleotides selected from large combinatorial pools of sequences for their capacity to efficiently recognize targets ranging from small molecules to proteins or nucleic acid structures. Like antibodies, they exhibit high specificity and affinity for target binding. As a result, they may display effective interference in biological processes, which renders them not only valuable diagnostic tools, but also promising therapeutic agents. In fact, one aptamer that inhibits human VEGF already received approval for the treatment of age-related macular degeneration, while several others are undergoing clinical trials. Aptamers display a large number of structural arrangements, which accounts for their binding efficiency and selectivity for unrelated targets. Among several architectures, the G-quadruplex (G-4) is adopted by several aptamers, the most popular of which shows inhibitory properties against thrombin, a pharmacologically relevant protein. G-4 structures consist of planar arrays of four guanines, each guanine pairing with two neighbours by Hoogsteen bonding. Recent work shows that G-4 arrangement is highly polymorphic and therefore represents a large family of stable structures with a common overall fold, but with well differentiated recognition elements that allow prominent diversity to be explored. Conformational plasticity consents fine tuning of target recognition as obtained by aptamer selection. Here, we will review the present knowledge on aptamers based on the G-4 structures and assess their diagnostic and therapeutic potential as biotech drugs for the detection and treatment of severe pathologies including vascular, cancer and viral diseases.
University of Padova, Department of Pharmaceutical Sciences, Via Marzolo, 5 - 35131 Padova, Italy.
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Gatto
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Palumbo
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Sissi
D000925:Anticoagulants / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000737:chemistry / Q000627:therapeutic use; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000627:therapeutic use; D001483:Base Sequence; D015195:Drug Design; D054856:G-Quadruplexes; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D014652:Vascular Diseases / Q000175:diagnosis / Q000188:drug therapy; D014777:Virus Diseases / Q000175:diagnosis / Q000188:drug therapy
D000925:Anticoagulants; D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D000998:Antiviral Agents; D052157:Aptamers, Nucleotide