# REGULATION OF BIOSYNTHESIS OF PROTEOGLYCAN

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1988 · $171,420

## Abstract

The overall objective of this research program is to elucidate the
mechanisms which regulate the synthesis of proteoglycans.  These
extracellular macromolecules, along with hyaluronic acid and collagen,
exhibit changing patterns in expression during development of cartilage
tissue.  As well, alterations in these components may underlie certain
disorders of cartilage, resulting in abnormal growth, development or
function.  Thus, understanding the mechanisms which control their
expression is a fundamental problem in connective tissue biochemistry.

Our specific aims include:  1) The determination of amino acid sequences
for selected regions of proteoglycan core proteins in order to identify
primary sequences around glycosylation sites, compare structures of
precursor forms and proteoglycans with different glycosaminoglycan
substituents and from different sources, and to synthesize specific
oligonucleotides in order to clone the core protein gene.  Core proteins
and subfragments are followed through isolation, deglycosylation, cleavage
and sequencing procedures immunologically with antibodies to core protein
and with a bioassay using xylosyltransferase acceptor activity; 2)
Elucidation of the temporal, topological and chemical events involved in
synthesis and processing of the core protein from the initially synthesized
precursors to the final secreted proteoglycan.  Localization and
characterization of the biosynthetic intermediate will involve metabolic
labeling, subcellular fractionation, in vitro glycosylation, and chemical
and immunological analysis, and 3) Certain aspects of the enzymes
responsible for initiation and processing of proteoglycans will also be
considered, as a complement to the structure and biosynthetic studies.  The
mechanism of action of xylosyltransferase will be examined with isolated
peptide fragments and synthetic peptides, and an active site-directed
covalent inhibitor of nucleotide sugars.  The PAPS synthesizing system will
be purified and structural relationship of components elucidated.

## Key facts

- **NIH application ID:** 3155059
- **Project number:** 5R01AR019622-12
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** NANCY B SCHWARTZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $171,420
- **Award type:** 5
- **Project period:** 1977-08-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155059

## Citation

> US National Institutes of Health, RePORTER application 3155059, REGULATION OF BIOSYNTHESIS OF PROTEOGLYCAN (5R01AR019622-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155059. Licensed CC0.

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