REVIEW ARTICLE
Synthesis and Purification of Highly Hydrophobic Peptides Derived from the C-Terminus of Amyloid β-Protein
M.M. Condron1, B.H. Monien1, G. Bitan2, 3, *
Article Information
Identifiers and Pagination:
Year: 2008Volume: 2
First Page: 87
Last Page: 93
Publisher ID: TOBIOTJ-2-87
DOI: 10.2174/1874070700802010087
Article History:
Received Date: 29/01/2008Revision Received Date: 09/03/2008
Acceptance Date: 09/03/2008
Electronic publication date: 27/3/2008
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Some biotechnological inventions involve expensive, sophisticated machines. Others are relatively simple innovations that nevertheless address, and solve difficult problems. Synthesis and purification of highly hydrophobic peptides can be a difficult and challenging task, particularly when these peptides have low solubility in both aqueous and organic solvents. Here we describe the synthesis and purification of a series of peptides derived from the hydrophobic Cterminus of the 42-residue form of amyloid β-protein (Aβ42), a peptide believed to be the primary cause for Alzheimer’s disease (AD). The series of C-terminal fragments (CTFs) had the general formula Aβ(x-42), x=28-39, which potentially can be used as inhibitors of Aβ42 assembly and neurotoxicity. Synthesis and purification of peptides containing 8-residues or less were straightforward. However, HPLC purification of longer peptides was problematic and provided <1% yield in particularly difficult cases due to very poor solubility in the solvent systems used both in reverse- and in normal phase chromatography. Modification of the purification protocol using water precipitation followed by removal of scavengers by washing with diethyl ether circumvented the need for HPLC purification and provided these peptides with purity as high as HPLC-purified peptides and substantially increased yield.
