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Aqueous self-assembly behaviour alteration derived from primary structure changes of model peptides

Bäcklund, Marcus LU (2020) KEMR30 20201
Department of Chemistry
Abstract
Understanding of the self-assembly behaviour of peptides is of great interest within several different areas such as neurodegenerative diseases, biotechnology, and peptide pharmaceuticals. In this work we have compared the impact on the self-assembly behaviour derived from systematic changes of the primary structure of A8K, where A denotes alanine and K lysine. Model peptides derived from A8K included in this work are KA8, G8K, and A4KA4, where G denotes glycine. In addition, we have also studied the self-assembly behaviour of binary mixtures of the model peptides to probe coaggregation of the different model peptides. To determine the aggregate structure small and wide-angle x-ray scattering and cryo TEM experiment were performed.... (More)
Understanding of the self-assembly behaviour of peptides is of great interest within several different areas such as neurodegenerative diseases, biotechnology, and peptide pharmaceuticals. In this work we have compared the impact on the self-assembly behaviour derived from systematic changes of the primary structure of A8K, where A denotes alanine and K lysine. Model peptides derived from A8K included in this work are KA8, G8K, and A4KA4, where G denotes glycine. In addition, we have also studied the self-assembly behaviour of binary mixtures of the model peptides to probe coaggregation of the different model peptides. To determine the aggregate structure small and wide-angle x-ray scattering and cryo TEM experiment were performed. Furthermore, to determine the secondary structure, we performed measurements using circular dichroism and infrared spectroscopy. We also probed the solubility of the model peptides through static light scattering experiments.
From our results we can derive, that replacing alanine with the less hydrophobic amino acid glycine leads to a higher critical aggregation concentration, as expected. Furthermore, the change removes much of the chirality of the model peptide, leaving lysine as the only chiral amino acid in the peptide. The result from this is that G8K form two-dimensional disc-like aggregates, whereas A8K aggregates into twisted one-dimensional fibres.
A higher peptide solubility is also observed for A4KA4 where the lysine amino acid has been placed in the middle of the peptide, presumably due to a destabilization of the laminated beta-sheet structure as the bulky lysine sidechain is accommodated within the peptide aggregates. By reversing the amino acids sequence, we observe a minor structural change for KA8. For the binary mixtures of A8K or KA8 and G8K, we can conclude that they coaggregate with aggregate properties reminiscent of the alanine model peptide. (Less)
Popular Abstract (Swedish)
Peptider är mindre versioner av protein. Det som man vanligtvis kan läsa på innehållsförteckningen på de flesta matvaror i dagen samhälle. Peptiderna i sig består av aminosyror som kan anses vara de minsta byggstenarna för peptider och proteiner.
Peptider och proteiner spelar en stor roll i våra biologiska system. Proteiner och peptider bidrar till flera viktiga processer. Proteiner hjälper till med att få vårt blod att koagulera när vi skadar oss. De kan hjälpa till med matsmältningen och mycket annat i kroppen.
Många processer i kroppen behöver ha peptider eller proteiner för att saker ska gå rätt till. Men det är inte alltid saker går som det ska. En alltför vanlig sjukdom vi har idag är Alzheimers.
Alzheimer och många andra... (More)
Peptider är mindre versioner av protein. Det som man vanligtvis kan läsa på innehållsförteckningen på de flesta matvaror i dagen samhälle. Peptiderna i sig består av aminosyror som kan anses vara de minsta byggstenarna för peptider och proteiner.
Peptider och proteiner spelar en stor roll i våra biologiska system. Proteiner och peptider bidrar till flera viktiga processer. Proteiner hjälper till med att få vårt blod att koagulera när vi skadar oss. De kan hjälpa till med matsmältningen och mycket annat i kroppen.
Många processer i kroppen behöver ha peptider eller proteiner för att saker ska gå rätt till. Men det är inte alltid saker går som det ska. En alltför vanlig sjukdom vi har idag är Alzheimers.
Alzheimer och många andra sjukdomar kan kopplas till proteiner och peptider där något går fel. För Alzheimers så börjar proteiner klumpa ihop sig för att något har gått fel vid tillverkningen av proteinerna.
Därav så finns det ett stort intresse av att förstå vilka faktorer som bidrar till hur peptider klumpar ihop sig. Därför så studerar detta arbete en serie av fyra konstgjorda modellpeptider. Varje peptid är framställd men en ändring sinsemellan. Detta för att kunna urskilja hur en liten ändring av modellpeptiden kan bidra till förändrat beteende i ett större perspektiv. (Less)
Please use this url to cite or link to this publication:
author
Bäcklund, Marcus LU
supervisor
organization
course
KEMR30 20201
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Model peptides, self-assembly, SAXS, FTIR, CD, physical chemistry, fysikalisk kemi
language
English
id
9027361
date added to LUP
2020-09-15 11:41:09
date last changed
2020-09-15 11:41:09
@misc{9027361,
  abstract     = {Understanding of the self-assembly behaviour of peptides is of great interest within several different areas such as neurodegenerative diseases, biotechnology, and peptide pharmaceuticals. In this work we have compared the impact on the self-assembly behaviour derived from systematic changes of the primary structure of A8K, where A denotes alanine and K lysine. Model peptides derived from A8K included in this work are KA8, G8K, and A4KA4, where G denotes glycine. In addition, we have also studied the self-assembly behaviour of binary mixtures of the model peptides to probe coaggregation of the different model peptides. To determine the aggregate structure small and wide-angle x-ray scattering and cryo TEM experiment were performed. Furthermore, to determine the secondary structure, we performed measurements using circular dichroism and infrared spectroscopy. We also probed the solubility of the model peptides through static light scattering experiments.
From our results we can derive, that replacing alanine with the less hydrophobic amino acid glycine leads to a higher critical aggregation concentration, as expected. Furthermore, the change removes much of the chirality of the model peptide, leaving lysine as the only chiral amino acid in the peptide. The result from this is that G8K form two-dimensional disc-like aggregates, whereas A8K aggregates into twisted one-dimensional fibres.
A higher peptide solubility is also observed for A4KA4 where the lysine amino acid has been placed in the middle of the peptide, presumably due to a destabilization of the laminated beta-sheet structure as the bulky lysine sidechain is accommodated within the peptide aggregates. By reversing the amino acids sequence, we observe a minor structural change for KA8. For the binary mixtures of A8K or KA8 and G8K, we can conclude that they coaggregate with aggregate properties reminiscent of the alanine model peptide.},
  author       = {Bäcklund, Marcus},
  keyword      = {Model peptides,self-assembly,SAXS,FTIR,CD,physical chemistry,fysikalisk kemi},
  language     = {eng},
  note         = {Student Paper},
  title        = {Aqueous self-assembly behaviour alteration derived from primary structure changes of model peptides},
  year         = {2020},
}