Multimeric glycotherapeutics: new paradigm

Glycoconj J. 2004;21(8-9):471-8. doi: 10.1007/s10719-004-5537-3.

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.

Publication types

  • Review

MeSH terms

  • Acrylic Resins / chemistry*
  • Acrylic Resins / pharmacology
  • Amino Sugars / chemistry
  • Antiviral Agents / chemistry
  • Bacterial Adhesion / drug effects
  • Glycopeptides / chemistry*
  • Glycopeptides / pharmacology
  • Humans
  • Orthomyxoviridae / drug effects*
  • Orthomyxoviridae / physiology
  • Receptors, Virus / chemistry*

Substances

  • Acrylic Resins
  • Amino Sugars
  • Antiviral Agents
  • Glycopeptides
  • Receptors, Virus
  • sialyl-N-acetyllactosamine
  • polyacrylamide