Book of abstracts version 5

Peptide synthesis for unravelling protein misfolding in
neurodegenerative diseases
Author
Femke van der Heijden
ATGM Academie voor Technologie Gezondheid en Milieu
Avans Hogeschool, Breda
of peptides for IR folding studies in the gas phase
University of Nijmegen
Abstract
Alzheimer’s, Huntington’s, Parkinson’s disease and fifteen other well-known neurodegenerative diseases are caused by
the misfolding and aggregation of proteins into abnormal and toxic species. The mechanism of t his process is shown in
figure 1 [1]. Since the tracking of the conformational change of the proteins is still a challenge, no sufficient cure is yet
been developed and thus more research needs to be done to cure millions of people from these protein mis folding
disorders. At the University of Nijmegen, the folding of proteins is studied using gas -phase infrared spectroscopy to
answer the question of why and how proteins form unwanted structures [2]. Three tripeptides are important structures
for this research, due to the ease of forming an aggregate. One of these tripeptides is l-lysyl-l-phenylalanyl-laspartic acid
(KFD), as shown in figure 2. KFD is the tripeptide which is most related to the so -called diseases, due to its high
aggregation properties. In this research, KFD is synthesized using a 5-step synthesis, including microwave assisted
coupling steps and traditional deprotecting steps. The coupling steps provide the attachment of the amino acids, while
the deprotecting steps provide for the reappearing of the significant carboxyl and amino groups in the wanted structure,
which where once protected to exclude side reactions [3]. After each coupling step the intermediary product is purified
using recrystallization and after every individual step, the product is characterized using FT-IR and LC-MS analysis.
Keywords: Proteopathy, Protein Misfolding, Alzheimer’s disease, IR Folding studies, Peptide synthesis.
Table of content
Figure 1: The Protein Misfolding and Aggregation Process .
Figure 2: Tripeptide ‘’KFD’’.
[1] E Herczenik en MFBG Gebbink, „Molecular and Cellular Aspects of Protein Misfolding and Disease,” The FSEB Journal,
2008, pp. 2115-2133.
[2] AM Rijs en J Oomens, Gas-Phase IR Spectroscopy and Structure of Biological Molecules, 2015, Switzerland : Springer
International Publishing.
[3] A Mahindra, KK Sharma en R Jain, „Rapid Microwave-Assisted Solution-Phase Peptide Synthesis,” Tetrahedron Letters,
2012, nr. 53, pp. 6931-6935.
71