H2020Индивидуална стипендия2015–2017

BARREL · Barrel Assemblies of Membrane Active Artificial Foldamers

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-08-01 → 2017-07-31
Финансиране от ЕС: 146 239 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Изкуствени молекули, подобни на пептидите, се тестват за способността им да взаимодействат с мастните мембрани на бактериите. Това помага за разработването на нови антибактериални средства, които да действат върху устойчиви или спящи клетки.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Barrel Assemblies of Membrane Active Artificial Foldamers

The sharp increase of microbial resistance against antibiotics is a global health threat, which have induced intensive research on antimicrobial agents. As persistent cells often become slow-growing or dormant, strategies targeting their membrane are becoming more relevant. In this respect, artificial assemblies of compounds with membrane activity and antimicrobial potential are thus highly interesting as potential new set of antibiotic agents. Considering that natural peptides with membrane activity are present in the innate immune system without resistance developed against them, these are interesting for development of novel antimicrobial compounds. Note, however, that bioavailability of these compounds is limited due to their sensitivity against degrading enzymes. Consequently, in recent decades an exponentially growing scientific interest is observed for peptidomimetic foldamers, which are peptide-based artificial compounds with structural diversity and folding properties often matching those of natural peptides. The membrane properties of these compounds however, is still poorly understood, therefore in the present proposal I aimed to develop and investigate non-natural foldamers that are capable of interacting with the lipid bilayer. Under the project period we have developed foldamers which readily interact with model membranes but at the same time are water soluble. Biophysical measurements also indicate, that these compounds oligomerize into preferentially beta-sheet rich assemblies, but do not form infinite fibrils. Based on these results we hope that this construct can be used in the future to develop novel non-natural species with antimicrobial potential.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Development of resistance by bacteria to antibiotics makes design of novel antimicrobial compounds increasingly important. As persistent cells often become slow-growing or dormant, strategies targeting their membrane are becoming more relevant. For several natural antimicrobial peptides function can be coupled to scaffolds with high sheet content. Toxic oligomers may assemble into hydrophilic or lipophilic sheet rich barrel constructs. However, this mechanism is not understood, greatly hindering rational development of similar compounds.My main research goal is to reach insight into the structure-function relationships of the barrel molecular scaffold and to gain understanding of how its ability to protect internal parts from the environment may contribute to toxicity. To approach this problem, I aim to design and study foldamer oligomer assemblies. I hope to define the fundamentals of how peptide - lipid bilayer interactions govern formation of potentially toxic oligomers at a molecular level. This may be exploited for developing new antimicrobial compounds.Foldamers are highly similar to natural peptides in terms of structural diversity, thus they are ideal model systems, in several cases showing antibiotic activity and enzyme resistance. The computationally designed, structures will be studied with experimental methods in model membranes. I have experience with theoretical (QM&MD) and experimental tools (polarized light spectroscopy). However, characterisation of solution phase membrane systems requires use of additional techniques and I aim to learn more into X-ray scattering methods (SAXS,WAXS). In the lab of Prof. Attila Bota, I will have optimal conditions to gain expertise with these. The Host Institute will also provide a professionally organized and equipped environment, where I would have excellent chances to be offered a tenured position. I expect that the results and the planned outreach activities will have a positive impact on EU research.

Оригинален текст от CORDIS (на английски).

Участници

HUN-REN TERMESZETTUDOMANYI KUTATOKOZPONT · BudapestКоординаторУнгария