Synthesis and conformational studies of N-glycosylated analogs of the HIV-1 principal neutralizing determinant

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DOIResolve DOI: http://doi.org/10.1021/bi00132a019
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TypeArticle
Journal titleBiochemistry
ISSN0006-2960
1520-4995
Volume31
Issue17
Pages42824288; # of pages: 7
AbstractThe principal neutralizing determinant (PND) of HIV-1 is found in the V, loop of the envelope glycoprotein. Antibodies elicited by peptides from this region, containing the GlyProGlyArgAlaPhe (GPGRAF) sequence, were able to neutralize diverse HIV-1 isolates [Javaherian et al. (1990) Science 250, 1590-1 5931, The GPGR tetrapeptide was predicted to adopt a type I1 j3-turn conformation. Earlier, we showed that glycosylation of synthetic T cell epitopic peptides at natural glycosylation sites stabilized @-turns [Otvas et al. (1991) Int. J. Pept. Protein Res. 38,467-4821, To evaluate the secondary structure modifying effect of the introduction of an N-glycosylated asparagine residue and to find a correlation between conformation and a possible PND potential, a series of glycopeptide derivatives, N(sugar)GPGRAFY-NH2 (4a-f), have been prepared, together with the parent peptides GPGRAFY-NH2 (2) and NGPGRAFY-NH2 (3), by solid-phase peptide synthesis [sugars: (a) j3-D-glucopyranosyl (Glc); (b) j3-D-galactopyranosyl (Gal); (c) Glc-j3( 1+4)-Glc; (d) 2-acetamido-2-deoxy-j3-~-glucopyranosyl (GlcNAc); (e) 2-acetamido-2-deoxyj3-D-galactopyranosyl (GalNAc); (f) GlcNAc-j3( 1+4)-GlcNAc; sugars are attached through a j3( l+N@) linkage to asparagine (N).] Peptides 2-4 were characterized by amino acid analysis, reversed-phase HPLC, and fast atom bombardment mass spectrometry. Circular dichroism (CD) and Fourier-transform infrared (FT-IR) spectroscopic studies were performed in trifluoroethanol (TFE) and water (D20 was used in FT-IR experiments). Nonglycosylated peptides showed significantly different CD spectra in aqueous and TFE solution. Moreover, a continuous spectral change was observed for all the peptides investigated when going from water to TFE. The chiral contribution of the aromatic side chains and acetamido sugars was also estimated. On the basis of CD and FT-IR evidence, the introduction of an N-glycosylated Asn residue does not destroy but rather stabilizes the suggested type I1 @-turn conformation of the PND peptide.
Publication date
PublisherAmerican Chemical Society
LanguageEnglish
AffiliationNRC Institute for Biodiagnostics; National Research Council Canada; NRC Steacie Institute for Molecular Sciences
Peer reviewedYes
NRC number375
NPARC number9148239
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Record identifier1ec0a056-055f-4fa4-a56a-ad7aab4ee410
Record created2009-06-25
Record modified2016-12-12
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