TY - JOUR
T1 - Non-natural glycosphingolipids and structurally simpler analogues bind HIV-1 recombinant gp120
AU - McReynolds, Katherine D.
AU - Bhat, Abhijit
AU - Conboy, John C.
AU - Saavedra, S. Scott
AU - Gervay-Hague, Jacquelyn
N1 - Funding Information:
Financial support for this research was gratefully received from NIH (AI40359-02), The American Foundation for AIDS Research (amfAR, 02669), Eli Lilly, Alfred P. Sloan Foundation, and The National Science Foundation Early Career Award (CHE9623583). K.D.M. gratefully acknowledges receipt of the University of Arizona Dean's Fellowship and the Department of Chemistry Carl S. Marvel Fellowship. We are indebted to Dr. Arpad Somogyi, director of the UA Mass Spectrometry Facility, for his assistance in compound characterization.
PY - 2002
Y1 - 2002
N2 - Interactions of recombinant gp120 (rgp120) with non-natural glycosphingolipids (GSLs) and structurally simpler analogues have been studied using a competitive adhesion assay. Conjugates of cellobiosyl ceramide and melibiosyl ceramide were synthetically prepared as water-soluble GSL analogues. These ligands were screened against a panel of biologically relevant analogues, and the results show that their interactions with rgp120 are comparable to natural cellular receptors. Glycolipid interactions with rgp120 were probed further by the synthesis and testing of structurally simpler analogues that were obtained by reductive amination of lactose, cellobiose, and melibiose with a biotinylated amino ethylene glycol moiety. RGp120 did not recognize conjugates lacking a lipid component. However, palmitoylation of the secondary amino alditols yielded compounds with comparable rgp120 affinity to the natural cellular receptor, galactosyl ceramide (GalCer). Taken together, the SAR showed that both a hydrophobic and a hydrophilic component are required for rgp120 recognition. Moreover, structural variability in the carbohydrate headgroup did not significantly alter rgp120 recognition indicating that this interaction is not highly specific.
AB - Interactions of recombinant gp120 (rgp120) with non-natural glycosphingolipids (GSLs) and structurally simpler analogues have been studied using a competitive adhesion assay. Conjugates of cellobiosyl ceramide and melibiosyl ceramide were synthetically prepared as water-soluble GSL analogues. These ligands were screened against a panel of biologically relevant analogues, and the results show that their interactions with rgp120 are comparable to natural cellular receptors. Glycolipid interactions with rgp120 were probed further by the synthesis and testing of structurally simpler analogues that were obtained by reductive amination of lactose, cellobiose, and melibiose with a biotinylated amino ethylene glycol moiety. RGp120 did not recognize conjugates lacking a lipid component. However, palmitoylation of the secondary amino alditols yielded compounds with comparable rgp120 affinity to the natural cellular receptor, galactosyl ceramide (GalCer). Taken together, the SAR showed that both a hydrophobic and a hydrophilic component are required for rgp120 recognition. Moreover, structural variability in the carbohydrate headgroup did not significantly alter rgp120 recognition indicating that this interaction is not highly specific.
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U2 - 10.1016/S0968-0896(01)00325-X
DO - 10.1016/S0968-0896(01)00325-X
M3 - Article
C2 - 11814851
AN - SCOPUS:0036155366
SN - 0968-0896
VL - 10
SP - 625
EP - 637
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 3
ER -