# N-LINKED OLIGOSACCHARIDES OF NORMAL AND MALIGNANT CELLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1992 · $250,268

## Abstract

In recent years, specific biological functions have been attributed
to modifications of the oligosaccharide units of glycoconjugates,
such as phosphorylation, O-acetylation and sulfation.  The long
term aimn of this program is to study modifications of N-linked
oligosaccharides and to understand their biological roles in helath
and disease.  We have discovered two novel classes of sulfated N-
linked oligosaccharides in mammalian cells.  The first is a class
of multiantennary complex-type oligosaccharides carrying Sialic
acids and O-Sulfate esters (SSOs) and the second is a family of N-
Linked molecules carrying Glycosaminoglycan-like chains attached
to complex-type oligosaccharides (NLGs).  This application proposes
to study the complete structures and biosynthesis of these novel
molecules, and to explore their biological roles.  The complete
structures will be elucidated using both labelled and unlabelled
matrials, by the production of monoclonal antibodies against unique
epitopes, and by the purification of specific sulfatases.
particular attention will be paid to the nature of the linkage
between the sulfated side chains and the core portion of the
oligosaccharide.  In selected cases, the nature of the proteins
carrying these molecules will also be investigated.  The effects
of para-nitrophenyl xyloside and of selected inhibitors of
processing glycosidases upon the biosynthesis of both types of
molecules will be explored.  The biosynthetic intermediates of
these molecules will be identified by labelling either intact Golgi
vesicles, cells at lowered temperature, or cells exposed to
monensin.  This will allow the prediction of the overall
biosynthetic pathways for the initiation and synthesis of both
types of chains.  Based upon all of the above, selected studies of
the enzymology of these pathways will be carried out.  In parallel
with these studies, we will examine further the structure and
biosynthesis of both SSOs and NLGs that we have found on a single
pancreatic tumor antigen.

The unusual nature of these structures suggests that they have
interesting biological roles.  Labelled SSOs will be used as
ligands to search for their cognate receptors in cell membranes.
Preliminary studies suggest that the LGs of pulmonary vascular
endothelial cells bind to Antithrombin III, and therefore, could
have a role in the control of thrombogenesis in the pulmonary
vasculature.  We will also compare the biological roles of the NLGs
with others already known for the more typical O-linked
heparin/heparan sulfate proteoglycans.  Other biological roles for
both types of structures may be predicted by the structural,
biosynthetic and receptor binding studies.  in the long run,
studies of these novel molecules may be of importance in such
diverse processes as the control of endothelial and smooth muscle
proliferation, the adhesion of tumor cells in the process of
metastases, and the control of thrombogenesis.

## Key facts

- **NIH application ID:** 3176917
- **Project number:** 5R01CA038701-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** AJIT P VARKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $250,268
- **Award type:** 5
- **Project period:** 1985-08-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176917

## Citation

> US National Institutes of Health, RePORTER application 3176917, N-LINKED OLIGOSACCHARIDES OF NORMAL AND MALIGNANT CELLS (5R01CA038701-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176917. Licensed CC0.

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