Caged amino acids for controlled release of bioactive compounds with light

• Autor(a) principal: Fernandes, Rita João Pereira
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/52583
• topic: Photochemistry; Photocaged biomolecules; Supramolecular chemistry; Host-guest interactions; Photocontrolled release; Spectroscopy; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

The use of conditional trigger signals presents advantages such as temporal and spatial control over molecules, which is especially interesting for controlling drug release events. Light is an ideal external trigger signal given the multitude of light sources available to exert that trigger. To make a light-responsive active compound it is usual to use the introduction of a photoremovable protecting group that makes it inactive until light action (caging). Macrocycles are one of the most well-known systems for carrying and releasing active compounds, mainly due to their increased solubility, bioavailability and stability. The cucurbit[n]uril (CB[n]) family is currently used for this purpose. These synthetic receptors are particularly attractive owing to their high affinity towards positively charged amphiphilic molecules which are the main characteristics of many drugs. The aim of this work was to develop a series of caged biomolecules as photoresponsive guests for development of supramolecular systems based on CB[7]/[8] capsules. Four amino acids (tryptophan, tyrosine, histidine and phenylalanine) and a tripeptide (FGG) were successfully caged and characterized by NMR spectroscopy. The host-guest interactions between CB[n]s and free/caged biomolecules were studied by techniques such as UV-Vis absorption and emission spectroscopies, NMR and ITC. Photodeprotection of caged compounds was monitored by UV-Vis. The potential of the photocontrolled release supramolecular system was tested by following the displacement of a probe. For CB[7] based system, tyrosine and FGG revealed as potential photoresponsive guests. For CB[8] based system, caged phenylalanine and tryptophan displayed no affinity towards the host cavity, which make them suitable photoresponsive guests for the release system. Lastly, it was found that CB[8]-caged FGG forms 1:1 complex, contrarily to CB[8]-FGG which forms a 1:2 complex, with association constants in the order of magnitude of 106 M-1 and 1011 M-2, respectively. This finding is promising for photocontrolled dimerization applications.