This highly glycosylated glycopeptide of human glycophorin AN
with Tn antigenic structures was synthesised. Glycophorin A is
the main transmembrane glycoprotein of erythrocytes responsible for the MN blood group specificity.
The glycopeptide has two glycosylation clusters with three and six adjacent glycosylation sites
and represents the N-terminal octadecapeptide of glycophorin AN.
A smaller glycopeptide, a part of the one shown, containing six adjacent glycosylation sites on a
decapeptide and a corresponding unglycosylated peptide were made for testing the synthesis and for
reference. The substances were fully characterised by CD and NMR spectroscopic techniques. This
includes the confirmation of the connectivity and some preliminary conformational indications. The
main techniques used were homonuclear TOCSY and NOESY spectra as well as HMQC and HMBC spectra for
13C-1H correlations. The
1H and 13C NMR data are the basis
for a more detailed conformational analysis in progress by the group of B. Meyer (Hamburg). The
conformation of the glycopeptides described here can be compared to that of the corresponding
unglycosylated peptide to give information on the influence of the first peptide-bound
N-acetyl-galactosamine unit on the shape of the glycoprotein.
Carbohydr. Res. 1997, 299, 33-48.
The immunodominant DTR motif of MUC1 tandem repeat peptide has been assumed to be exposed during
development of breast cancer due to a site-specific non-glycosylation. The binding of a series of
DTR specific antibodies is strongly enhanced if the motif is glycosylated. Thirty monoclonal
anti-MUC1 antibodies with a DTR specificy were tested for binding to this tandem repeat peptide
and other (not shown) O-glycosylated with Tn antigenic structure.
Binding was measured in ELISA experiments by the groups of F. G. Hanisch (Köln) and S. Goletz
(Berlin). Cancer Res. 1998, 58, 2541-2549. The substances were fully
characterised by CD and NMR spectroscopic techniques. This includes the confirmation of the
connectivity and secondary structure conformational analysis. The main techniques used were
homonuclear TOCSY and NOESY spectra as well as HMQC and HMBC spectra for
Binding of the HIV-1 external envelope glycoprotein gp120 to the CD4 receptor on human cells is
the first step in HIV:cell interaction and virus entry. After attachment to CD4, gp120 interacts
with one of the chemokine receptors CCR5 or CXCR4, recently identified as the major coreceptors
for HIV-1. It was shown that the interaction between gp120 and the two coreceptors is mediated by
the third variable region (V3 loop) of gp120. Mutational studies with the V3 loop did suggest that
coreceptor usage and HIV:cell fusion are linked to V3 loop amino acid sequences. Thus, in a second
step, the V3 loop may interact with the chemokine receptor to permit HIV:cell fusion. This second
step of HIV:cell interaction can be inhibited by synthetic V3 loop peptides containing the highly
conserved GPGRAF-motif of the subtype B strains. Since gp120 and especially the V3 loop is highly
glycosylated, the synthesis of glycosylated V3 loop peptides and the influence of glycosylation on
the three dimensional structure of the V3 loop peptide is in focus.The moderate metabolic stability
of glycopeptides limits their potential as therapeutic agents, modified analogs such as e.g.
glycopeptides containing C-glycosylated amino acids have been reported. The glucositoyl-amino acid
unit as a mimetic of N4-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-L-asparagin was synthesised by A.
Schäfer (Hamburg). The potential anti-HIV active is characterized by a new amide linkage
between the 2-amino function of the carbohydrate moiety and the side chain of the amino acid which
ensures an improved stability towards enzymes, acids and bases, in contrast to a labile N-glycosidic
linkage. Biochemical aspects are examinated by M. Schreiber (Hamburg). The substance is
characterised by NMR spectroscopic techniques. This includes the confirmation of the connectivity
and secondary structure conformational indications. The techniques used were homonuclear TOCSY and
NOESY spectra for 1H-1H correlations.
Carbohydr. Res. 1998, 313, 107-116.