Characterisation of Model Peptides QKFFFDQ and QDFFFKQ, and the Effect of Modification with Myristic Acid and Biphenyl-4-Carboxylic Acid
Authors
Smedt, Rasmus Müller ; Nguyen, Tin Duy
Term
4. term
Education
Publication year
2019
Submitted on
2019-06-10
Pages
49
Abstract
Peptidbaserede lægemidler har ulemper, blandt andet at de ofte nedbrydes hurtigt i kroppen. Syntetiske ændringer kan hjælpe med at mindske disse problemer. I dette studie blev to peptider, QDFFFKQ og QKFFFDQ, baseret på modelpeptidet RFFFR, bekræftet at danne fibriller i polære opløsningsmidler. Peptiderne blev modificeret med myristinsyre og biphenyl-4-carboxylsyre, tilføjet under fastfase-peptidsyntese via en in situ-esterificering. Målinger med cirkulær dikroisme og fluorescens tyder på, at peptiderne stabiliseres af π-stabling (stabling af aromatiske ringe). Atomkraftmikroskopi (AFM) viste en markant øget tendens til fibrillering for begge peptider efter modifikation med enten myristinsyre eller biphenyl-4-carboxylsyre. Modifikationerne gav dog en betydelig lavere opløselighed i vandige miljøer, hvilket kan være problematisk for anvendelse i lægemidler. Derfor bør mindre hydrofobe grupper undersøges.
Peptide-based medicines often have drawbacks, including breaking down quickly in the body. Synthetic modifications can help address these issues. In this study, two peptides, QDFFFKQ and QKFFFDQ, derived from the model peptide RFFFR, were confirmed to form fibrils in polar solvents. The peptides were modified with myristic acid and biphenyl-4-carboxylic acid by adding these groups during solid-phase peptide synthesis using an in situ esterification step. Circular dichroism and fluorescence measurements indicate that the peptides are stabilized by pi-stacking (stacking interactions between aromatic rings). Atomic force microscopy (AFM) showed a significant increase in the tendency to fibrillate for both peptides after modification with either myristic acid or biphenyl-4-carboxylic acid. However, the modifications also greatly reduced solubility in water, which could hinder pharmaceutical use. Therefore, less hydrophobic modifications should be explored.
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