Glycodendriticstructures

(promising new antiviral drugs)

Dendrimers

1.Dendrimers are the macromolecules with a well defined globular shape and were synthesized first during the end of 1970's. These are sophisticated and also curious molecules and they have attracted interest of the chemists owing to their potential applications in many areas, like catalysis, material science and also biomedicine. (1)

2.At present dendrimers are being used as the carrier molecules for the drug delivery and also gene transfer, also as catalysts in the homogeneous catalysis and as scaffolds in order to accomplish the multivalent presentations of ligands with an interesting biological application. (1)

3.One of most attractive applications in biomedical field is use of functionalized dendrimers as the antiviral agents. These so called dendrimers are able to form many stable complexes with that of viral structures or receptors at cell surface, resulting in the disruption of virus-cell interactions during infection process. (1)

4.We can highlight the dendrimers based on polyamidoamine (PAMAM) assistance. These PAMAM scaffolds are functionalized with the negatively charged molecules in order to generate poly anion structures that are able to interact with the viral envelope glycoproteins, hence preventing the binding of the viruses (HIV) or (HSV) to surface of target cells. These have been tested in vitro for HIV and HSV and in vivo for HSV in guinea pig and mice models and may be considered as promising candidates as microbicides after required formulation. (1)

1.Glycodendrimers, which are the dendrimers present at their surface, multiple copies of the carbohydrates, were recently developed and are the excellent tools to address the carbohydrate-protein interactions in the biological processes at molecular level and also in order to study the multivalent effect. (2)

2.Carbohydrates confer high selectivity in order to interact with the specific lectin receptors, however, until now, few glycodendrimers have been found in the biomedical applications. For example, one of these applications helps these molecules to interact with Fimbrae proteins in order to avoid infection by E.coli. (2)

3.Another example is a 4th-generation PAMAM dendrimer conjugated with that of sialic acid. These sialic acids are present at the dendrimer surface and are able to interact with the haemagglutinin, the which is the major surface glycoprotein of influenza A virus, and prevents the viral adhesion to the target cells that exhibits sialic acid at their surface. (2)

4.This activity was tested in vitro and in vivo by using a murine influenza pneumonitis model. (2)

1.We have seen the possibility of using the glycodendritic compounds as the most potential drugs that are able to block the binding of the pathogenic glycoproteins to DC-SIGN. As a multivalent scaffold, we have selected a hyperbranched dendritic polymer named as Boltorn, of which 2^nd,3^rd and 4^th generations are commercially available at very low price. (2)

2.These polymers are conveniently functionalized with monosaccharide mannose. We have demonstrated that glycodendritic structures, based on a Boltorn polymer of 2^nd and 3^rd generations, and these are perfectly soluble in the physiological conditions, are non-toxic against many of the cell lines and easy to prepare.

3.Hence, testing their biological activity as an anti-adhesive molecule that blocks the cell receptor DC-SIGN looks a promising chance. (2)

4.These preliminary results supports the potential application of these systems as antiviral compounds. Research to address the bioavailability and stability of Boltorn-based glycodendrimers is currently in progress.

5.In case if these glycodendritic structures are recognized and degraded by mannosyl glycosylases, we have envisaged as a strategy the use of mimic carbohydrates that interact with a receptor but that are not recognized by hydrolytic enzymes. (2)

Top: it is a chemical structure of a 2nd -generation Boltorn hyperbranched dendritic polymer--BoltornH20;bottom: a 3rd-generation Boltorn hyperbranched dendritic polymer--BoltornH30.(1)

REFERENCES:

1.http://jac.oxfordjournals.org/content/54/3/579.full (accessedon29^thOctober2011,10:20pm)

2.http://www.febsletters.org/article/S0014-5793(98)00340-8/abstract (accessedon29^thOctober2011,10:20pm)

"THIS BLOG IS FREE FROM PLAGIARISM"

m.sandhyasravya@gmail.com

"PHARMA WARRIORS"