# CONFORMATION OF PHOSPHORYLATED BRAIN PEPTIDES

> **NIH NIH R01** · WISTAR INSTITUTE · 1991 · $128,747

## Abstract

Alzheimer's disease (AD) and some other neurodegenerative diseases are
characterized by a progressive accumulation of neurofibrillary tangles
(NFT) and amyloid-rich senile plaques (SP).  Although not restricted to AD,
the number of SPs and NFTs correlates with the severity of dementia.  The
tangles are most probably formed from tau, a microtubule-associated
protein, and other brain proteins, like neurofilaments (NFs).  We
identified a serine residue on human tau which, when phosphorylated,
changes the normal protein to A68, a group of polypeptides that are AD-
specific and present in NFTs.

We also demonstrated that in certain circumstances, phosphorylation changes
the conformation of synthetic peptides corresponding to human NF and tau
from a helical-turn structure to beta-pleated sheets that are
characteristic of the tangles at the electron microscopic level.
Phosphorylation probably also plays a vital role in the function,
transport, degradation, etc., of these and other neuronal cytoskeletal
proteins.  The phosphorylation sites of NF and tau are embedded in similar
amino acid regions and have a high metal ion binding potential.

We propose to synthesize non-phosphorylated and phosphorylated peptides
corresponding to normal and abnormal phosphorylation sites of human tau
protein.  We will use circular dichroism (CD), nuclear magnetic resonance
(NMR) and Fourier-transform infrared (FT-IR) spectroscopy to determine the
conformation of the peptides in different solvents and environmental
conditions.  We are looking for phosphate acceptor sites that may serve as
cores for intermolecular aggregate formation after abnormal post-
translational modifications have changed the conformation.  We also propose
to extend these studies to those fragments of NF that abet the deposition
of tau and thereby give rise to the known microscopic structure of NFTs.
These studies will give insights into the topographical and environmental
requirements for deposits of abnormal proteins in AD.

## Key facts

- **NIH application ID:** 3122595
- **Project number:** 1R01AG010670-01
- **Recipient organization:** WISTAR INSTITUTE
- **SAM.gov UEI:** DW1XZMGNFBL4
- **Principal Investigator:** LASZLO OTVOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $128,747
- **Award type:** 1
- **Project period:** 1991-09-29 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122595

## Citation

> US National Institutes of Health, RePORTER application 3122595, CONFORMATION OF PHOSPHORYLATED BRAIN PEPTIDES (1R01AG010670-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122595. Licensed CC0.

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