title: Multimeric glycotherapeutics: new paradigm.
abstract: The general principle of anti-adhesion therapy is the inhibition of microorganism adhesion to the host cell with the help of a soluble receptor analog. Despite an evident attractiveness of the concept and its long existence, the therapeutics of the 'post-antibiotic era' have not yet appeared. This can be explained by the contradictoriness of requirements for anti-adhesion drugs: to be efficient a drug must be multivalent, i.e. large molecule, but to obtain FDA approval it should be a small molecule. A way to overcome this contradiction is self-assembly of glycopeptides. The carbohydrate part of glycopeptide is responsible for binding with the lectin of microorganisms, whereas a simple peptide part is responsible for an association to the so-called tectomers. Depending on the structure, tectomers are formed either spontaneously or upon promotion of a microorganism. In particular, sialopeptide, which is capable of converting to a tectomer only in the presence of the influenza virus, has been obtained. Thus, the new strategy of anti-adhesion therapy can be formulated as follows: (1) identification of oligosaccharide-receptor for a particular virus (bacteria); (2) optimization of the peptide part; (3) conventional trials. The expected advantages of this strategy are the following: (i) no polymer; (ii) a virion completely covered with a tectomer, i.e. blocking is both complete and irreversible; (iii) rapid and rational lead identification and optimization; (iv) minimum side effects; (v) potential for microorganism resistance to natural receptor is lower than in the case of mimetics.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, Moscow V-437, 117997, Russia, bovin@carbohydrate.ru
authors.forename: Nicolai V
authors.initials: NV
authors.lastname: Bovin
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Tuzikov
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Chinarev
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Gambaryan
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry* / Q000494:pharmacology; D000606:Amino Sugars / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry; D001422:Bacterial Adhesion / Q000187:drug effects; D006020:Glycopeptides / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000502:physiology; D011991:Receptors, Virus / Q000737:chemistry*; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000606:Amino Sugars; D000998:Antiviral Agents; D006020:Glycopeptides; D011991:Receptors, Virus; D000099166:Polyacrylamides; C032269:sialyl-N-acetyllactosamine