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Evaluation of the synthesis of sialic acid-PAMAM glycodendrimers without the use of sugar protecting groups, and the anti-HIV-1 properties of these compounds.

Publication ,  Journal Article
Clayton, R; Hardman, J; LaBranche, CC; McReynolds, KD
Published in: Bioconjug Chem
October 19, 2011

A study was undertaken to evaluate the feasibility of synthesizing six sialic acid-PAMAM glycodendrimers using unprotected sialic acid in as few as 1-4 steps using two different reaction pathways, and to assess the sulfated derivatives for anti-HIV activity. The syntheses were accomplished through either the direct attachment of the sialic acid carboxyl group to amine-terminated PAMAM (a divergent-like approach) using BOP coupling, or by first reacting sialic acid with a polar bifunctional spacer molecule, attaching the sugar-linker to carboxy-terminated PAMAM (a convergent-like approach), and again using BOP-mediated coupling reactions. It was hypothesized that the latter approach would be the most successful method, as any steric congestion between the sialic acid and the PAMAM would be minimized using an intervening polar linker. However, the divergent-like synthesis proved to be the superior method, resulting in 11.4%, 14%, and 28% of the fully substituted generations 0, 1, and 2 sialic acid-PAMAM conjugates, respectively, as compared to 6.4% of only the generation -0.5 sialic acid-linker-PAMAM conjugate for the convergent-like method. Upon sulfation of the four glycodendrimers, binding capabilities to the recombinant HIV protein, gp120, were assessed using an ELISA assay. Compounds that showed promising binding characteristics were then further assessed for inhibition of HIV-1 infection using a well-characterized luciferase reporter gene neutralization assay. The generation 2 sulfated sialic acid-PAMAM glycodendrimer, sulfo-6, bearing 16 sialic acids with 11 sulfate groups incorporated at 4.03% sulfur content by weight, was found to inhibit all four HIV-1 strains tested in the low micromolar range.

Duke Scholars

Published In

Bioconjug Chem

DOI

EISSN

1520-4812

Publication Date

October 19, 2011

Volume

22

Issue

10

Start / End Page

2186 / 2197

Location

United States

Related Subject Headings

  • Organic Chemistry
  • N-Acetylneuraminic Acid
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • Dendrimers
  • Anti-HIV Agents
  • 3404 Medicinal and biomolecular chemistry
  • 3101 Biochemistry and cell biology
 

Citation

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Clayton, R., Hardman, J., LaBranche, C. C., & McReynolds, K. D. (2011). Evaluation of the synthesis of sialic acid-PAMAM glycodendrimers without the use of sugar protecting groups, and the anti-HIV-1 properties of these compounds. Bioconjug Chem, 22(10), 2186–2197. https://doi.org/10.1021/bc200331v
Clayton, Russell, Janee Hardman, Celia C. LaBranche, and Katherine D. McReynolds. “Evaluation of the synthesis of sialic acid-PAMAM glycodendrimers without the use of sugar protecting groups, and the anti-HIV-1 properties of these compounds.Bioconjug Chem 22, no. 10 (October 19, 2011): 2186–97. https://doi.org/10.1021/bc200331v.
Clayton, Russell, et al. “Evaluation of the synthesis of sialic acid-PAMAM glycodendrimers without the use of sugar protecting groups, and the anti-HIV-1 properties of these compounds.Bioconjug Chem, vol. 22, no. 10, Oct. 2011, pp. 2186–97. Pubmed, doi:10.1021/bc200331v.
Journal cover image

Published In

Bioconjug Chem

DOI

EISSN

1520-4812

Publication Date

October 19, 2011

Volume

22

Issue

10

Start / End Page

2186 / 2197

Location

United States

Related Subject Headings

  • Organic Chemistry
  • N-Acetylneuraminic Acid
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • Dendrimers
  • Anti-HIV Agents
  • 3404 Medicinal and biomolecular chemistry
  • 3101 Biochemistry and cell biology