Non-natural glycosphingolipids and structurally simpler analogues bind HIV-1 recombinant gp120

Katherine D. McReynolds, Abhijit Bhat, John C. Conboy, S. Scott Saavedra, Jacquelyn Gervay-Hague

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)625-637
Number of pages13
JournalBioorganic and Medicinal Chemistry
Volume10
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Glycosphingolipids
Ceramides
HIV-1
Melibiose
Lipoylation
Galactosylceramides
Sugar Alcohols
Amination
Cellobiose
Ethylene Glycol
Glycolipids
Lactose
Assays
Adhesion
Carbohydrates
Ligands
Lipids
Water
Testing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Non-natural glycosphingolipids and structurally simpler analogues bind HIV-1 recombinant gp120. / McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra, S. Scott; Gervay-Hague, Jacquelyn.

In: Bioorganic and Medicinal Chemistry, Vol. 10, No. 3, 2002, p. 625-637.

Research output: Contribution to journalArticle

McReynolds, Katherine D. ; Bhat, Abhijit ; Conboy, John C. ; Saavedra, S. Scott ; Gervay-Hague, Jacquelyn. / Non-natural glycosphingolipids and structurally simpler analogues bind HIV-1 recombinant gp120. In: Bioorganic and Medicinal Chemistry. 2002 ; Vol. 10, No. 3. pp. 625-637.
@article{87abc992454c49a29c3c678b18ada18f,
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.",
author = "McReynolds, {Katherine D.} and Abhijit Bhat and Conboy, {John C.} and Saavedra, {S. Scott} and Jacquelyn Gervay-Hague",
year = "2002",
doi = "10.1016/S0968-0896(01)00325-X",
language = "English (US)",
volume = "10",
pages = "625--637",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "3",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=0036155366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036155366&partnerID=8YFLogxK

U2 - 10.1016/S0968-0896(01)00325-X

DO - 10.1016/S0968-0896(01)00325-X

M3 - Article

C2 - 11814851

AN - SCOPUS:0036155366

VL - 10

SP - 625

EP - 637

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 3

ER -