Design and synthesis of self-assembling peptides with binding affinity to hyaluronan

Abstract

Hyaluronan (HA) is a natural polymer that due to its viscoelasticity, good biocompatibility and a conformational flexibility, has been a polysaccharide of great interest to the scientists that is used in various biomedical and clinical applications such as tissue engineering, biomaterials engineering and cosmetics. This project aimed to explore the self-assembly between hyaluronan (HA) and HA-binding peptides derived from Pep-1[NH2-GAHWQFNALTVR-NH2], a peptide known to bind HA and identified by phage display. Six variations of Pep-1 were synthesized to test if they can form new nanostructures with HA. Peptides with alkyl chains allow the formation of highly stable self-assembled nanostructures. Considering this fact, were synthesized four peptides with these properties in order to try the interaction between them and hyaluronan. On the other hand, thiols (compounds that contain a SH group) can bond to gold due to the capability to be chemisorbed on metal surfaces, forming a very stable metal-sulfur bonds. Therefore, it was synthesized a peptide with a tail constituted by Mercaptoethanol acid that is expected to react with gold, displaying the Pep-1 free to interact with HA. Electrospray Ionization Mass Spectrometry and High-Performance Liquid Chromatography techniques were used to characterize and purify the peptides, respectively. After the experimental work and its results, it was concluded that by increasing the percentage of Pep-1 is possible to see an interaction between it and hyaluronan. Peptides with longer alkyl chain are to hydrophobic to be purified and consequently it was impossible to study the interaction between them and HA.When the alkyl chains become shorter, the peptides become less hydrophobic and their purification is possible. Though, the peptides with shorter chains can´t allow the formation of self-assembled structures. The peptide that has a Mercaptoethanol acid is hydrophobic but, its purification is possible. More tests should be done in order to study and analyze if the interaction between this last peptide and HA is possible.

Date of Award	6 Jul 2017
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Helena Azevedo (Supervisor) & Dominic Collis (Co-Supervisor)