Cyclic dipeptides and their self-assembling properties

Balangtaa, Jacob

Abstract

Over recent years, cyclic dipeptides, or 2,5-diketopiperazines, have found numerous applications in nanotechnology, such as biological drug delivery. Reasons for this include their ease of synthesis and numerous intrinsic properties. One such property is self-assembly, wherein the cyclic dipeptide can undergo molecular reorganisation in certain conditions, and exhibit a novel structure. This reorganisation can be achieved in different ways; the results often vary depending on the original conditions.
A popular method of synthesising linear dipeptides is through solid phase peptide synthesis, which has numerous advantages compared to the older solution phase method. In this project, Fmoc solid phase peptide synthesis (SPPS) was employed to synthesise four different linear dipeptides, and their cyclisation and subsequent self-assembly probed in different solvents. The dipeptides used were chosen based on their varying aromatic side-chains, whilst solvents of varying polarities were utilised.
Linear dipeptides were added to the solvents, and it was seen that many of them were insoluble in certain solvents. The ones that did dissolve were heated and tested for unconventional cyclisation. Cyclic dipeptide analogues from the initial sequences H-FF-OH, H-HH-OH, H-HF-OH and H-HY-OH were confirmed and found to have a self-assembled structure in each solvent they originated from. Cyclic FF (cFF, cyclised from linear H-FF-OH), self-assembled in the most number of solvents, and produced a similar structure in each of them. In addition, cyclic FF that self-assembled in 1,4-dioxane was found to have blue-luminescent properties. It was also observed that the amount of self-assembly was affected by the temperature each solvent containing the peptide was subjected to. cHH self-assembled in only one solvent, n-PrOH, whereas cHF and cHY both self-assembled in i-PrOH and THF. Self-assembled cFF was observed to be made of rod-like strands whereas self-assembled cHH appeared to be composed of a hierarchal structure consisting of needle-like components in an “urchin-like” sphere. Self-assembled cHF and cHY had a mixture of structures derived from those seen in cFF and cHH, with a notable flower-like entity seen for cHY self-assembled in THF.

Citation

Balangtaa, J. (2017). Cyclic dipeptides and their self-assembling properties. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4224589

• Thesis Type: Thesis
• Deposit Date: Jan 5, 2023
• Publicly Available Date: Feb 24, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4224589
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: May 1, 2017