Abstract
The β‐amyloid peptide (Aβ) is the major constituent of senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. Recently a post‐translationally modified analogue of the human β‐amyloid peptide, which contains isoaspartatic residues in positions 1 and 7, was isolated from parenchyma and leptomeningeal microvasculature of Alzheimer's disease patients [Roher, A. E., Lowenson, JD., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zürcher‐Neely, H. A., Heinrikson, R. L., Ball, M. J. & Greenberg, B. D. (1993) J. Biol. Chem. 268, 3072–3083]. We used circular dichroism and Fourier‐transform infrared spectroscopy to characterize the conformational changes on human Aβ upon substitution of Asp1 and Asp7 to isoaspartic residues. We found that the intermolecular β‐pleated‐sheet content is markedly increased for the post‐translationally modified peptide compared to that in the corresponding unmodified human or rodent Aβ sequences both in aqueous solutions in the pH 7–12 range, and in membrane‐mimicking solvents (such as aqueous octyl‐β‐d‐glucoside or aqueous acetonitrile solutions). These findings underline the importance of the originally α‐helical N‐terminal regions of the unmodified Aβ peptides in defining its secondary structure and may offer an explanation for the selective aggregation and retention of the isomerized Aβ peptide in Alzheimer's‐disease‐affected brains.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 959-964 |
| Number of pages | 6 |
| Journal | European Journal of Biochemistry |
| Volume | 221 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 1994 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Synthetic post‐translationally modified human Aβ peptide exhibits a markedly increased tendency to form β‐pleated sheets in vitro. / FABIAN, Heinz; SZENDREI, Gyorgyi I.; MANTSCH, Henry H.; Greenberg, Barry; ÖTVÖS, Laszlo.
In: European Journal of Biochemistry, Vol. 221, No. 3, 01.01.1994, p. 959-964.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Synthetic post‐translationally modified human Aβ peptide exhibits a markedly increased tendency to form β‐pleated sheets in vitro
AU - FABIAN, Heinz
AU - SZENDREI, Gyorgyi I.
AU - MANTSCH, Henry H.
AU - Greenberg, Barry
AU - ÖTVÖS, Laszlo
PY - 1994/1/1
Y1 - 1994/1/1
N2 - The β‐amyloid peptide (Aβ) is the major constituent of senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. Recently a post‐translationally modified analogue of the human β‐amyloid peptide, which contains isoaspartatic residues in positions 1 and 7, was isolated from parenchyma and leptomeningeal microvasculature of Alzheimer's disease patients [Roher, A. E., Lowenson, JD., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zürcher‐Neely, H. A., Heinrikson, R. L., Ball, M. J. & Greenberg, B. D. (1993) J. Biol. Chem. 268, 3072–3083]. We used circular dichroism and Fourier‐transform infrared spectroscopy to characterize the conformational changes on human Aβ upon substitution of Asp1 and Asp7 to isoaspartic residues. We found that the intermolecular β‐pleated‐sheet content is markedly increased for the post‐translationally modified peptide compared to that in the corresponding unmodified human or rodent Aβ sequences both in aqueous solutions in the pH 7–12 range, and in membrane‐mimicking solvents (such as aqueous octyl‐β‐d‐glucoside or aqueous acetonitrile solutions). These findings underline the importance of the originally α‐helical N‐terminal regions of the unmodified Aβ peptides in defining its secondary structure and may offer an explanation for the selective aggregation and retention of the isomerized Aβ peptide in Alzheimer's‐disease‐affected brains.
AB - The β‐amyloid peptide (Aβ) is the major constituent of senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. Recently a post‐translationally modified analogue of the human β‐amyloid peptide, which contains isoaspartatic residues in positions 1 and 7, was isolated from parenchyma and leptomeningeal microvasculature of Alzheimer's disease patients [Roher, A. E., Lowenson, JD., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zürcher‐Neely, H. A., Heinrikson, R. L., Ball, M. J. & Greenberg, B. D. (1993) J. Biol. Chem. 268, 3072–3083]. We used circular dichroism and Fourier‐transform infrared spectroscopy to characterize the conformational changes on human Aβ upon substitution of Asp1 and Asp7 to isoaspartic residues. We found that the intermolecular β‐pleated‐sheet content is markedly increased for the post‐translationally modified peptide compared to that in the corresponding unmodified human or rodent Aβ sequences both in aqueous solutions in the pH 7–12 range, and in membrane‐mimicking solvents (such as aqueous octyl‐β‐d‐glucoside or aqueous acetonitrile solutions). These findings underline the importance of the originally α‐helical N‐terminal regions of the unmodified Aβ peptides in defining its secondary structure and may offer an explanation for the selective aggregation and retention of the isomerized Aβ peptide in Alzheimer's‐disease‐affected brains.
UR - http://www.scopus.com/inward/record.url?scp=0028220163&partnerID=8YFLogxK
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U2 - 10.1111/j.1432-1033.1994.tb18811.x
DO - 10.1111/j.1432-1033.1994.tb18811.x
M3 - Article
C2 - 8181478
AN - SCOPUS:0028220163
VL - 221
SP - 959
EP - 964
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 3
ER -