Document Detail


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.
MedLine Citation:
PMID:  21859137     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Russell Clayton; Janee Hardman; Celia C LaBranche; Katherine D McReynolds
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-09-06
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  22     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-19     Completed Date:  2012-02-07     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2186-97     Citation Subset:  IM    
Affiliation:
Department of Chemistry, California State University, Sacramento, California 95819-6057, United States.
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / chemistry*,  pharmacology*
Dendrimers / chemistry*,  pharmacology*
HIV Envelope Protein gp120 / metabolism
HIV Infections / drug therapy
HIV-1 / drug effects*
Humans
N-Acetylneuraminic Acid / chemistry*,  pharmacology*
Grant Support
ID/Acronym/Agency:
1R15AI068444-01/AI/NIAID NIH HHS; AI30034/AI/NIAID NIH HHS; P51 RR000166/RR/NCRR NIH HHS; R15 AI068444-01/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Dendrimers; 0/HIV Envelope Protein gp120; 0/PAMAM Starburst; 131-48-6/N-Acetylneuraminic Acid
Comments/Corrections

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