title: Non-natural glycosphingolipids and structurally simpler analogues bind HIV-1 recombinant Gp120.
abstract: 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.
authors.affiliation: Department of Chemistry, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: McReynolds
authors.forename: Abhijit
authors.initials: A
authors.lastname: Bhat
authors.forename: John C
authors.initials: JC
authors.lastname: Conboy
authors.forename: S Scott
authors.initials: SS
authors.lastname: Saavedra
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Gervay-Hague
mesh_terms: D001667:Binding, Competitive; D006028:Glycosphingolipids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D006028:Glycosphingolipids; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins