PEPREP · Peptide based self-replicating coacervate protocells
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-07-16 → 2021-07-31
- Финансиране от ЕС
- 187 572 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Протоклетките се създават чрез прости молекули от кратки пептиди, като например комбинация от дифенилаланин и специален свързващ елемент. Това помага за по-лесното разбиране на процесите по сглобяване на първите живи структури и техния произход.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Peptide based self-replicating coacervate protocells
The main challenge in designing the coacervates-based protocells in the chemistry laboratory is the complexity in the constituting building blocks of design protocells. Usually, these complex coacervates are formed from the combination of two components, which are bigger in molecular weight and give rise to the complex understanding of their assembly process being used for the protocell studies. Recently, it has been observed that many research groups are developing minimal biomolecules for the formation of complex coacervates, which could be used as a protocell model. They are mainly focussing on the simple and short motifs including nucleotide bases, short peptides, and metals to make the complex coacervates with traditional electrostatic interaction. There are main three problems in the complex coacervates systems: 1) structural complexity, 2) longer and bigger molecules rise the difficulties to understand the formation process, 3) they are mostly not prebiotic relevant. By keeping the challenges in mind, our ultimate goal was to design and synthesize the simplest single molecule-based coacervates to make the protocells in the laboratory. Our design is made of short peptide derivatives and can be synthesized accurately with great reproducibility in four steps in an ordinary chemistry laboratory. We prepared several derivatives with a sticker-spacer model approach, where we use the hydrophobic amino acids as stickers and different spacers as linkers between two stickers. The model compound (FFssFF) was formed with diphenylalanine (FF)-spacer as the apolar motif and disulfide linker (cystamine) as a spacer as the polar motif. The model compound is soluble in water and on increasing the pH it forms the coacervates and looks like a turbid solution in the vial and was confirmed under the microscope. The project has set the foundational work for an entirely new direction and these results will benefit society with a great impact in the future. The main objectives of this project were divided into four steps, which correspond to respective work packages (WPs). The following are the brief objectives of the project. 1- Design and synthesis of the peptide derivatives 2- Coacervation, Different linkers with different physical and chemical properties, including the different chemistries of linkers for replication 3- Encapsulation of macromolecules into coacervates 4- Coacervates as microreactors and coacervates to vesicle transition
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
One of the most fundamental questions in chemistry and biology is how a self-replicating protocell could form from collection of inanimate molecules. Self-replicating RNA molecules in lipid compartments have been widely studied, but these systems are inherently unstable and a plausible mechanism for their spontaneous formation and repeated replication is still lacking. Here, I propose to use coacervation of self-templating peptides as a radically new approach to create stable self-replicating protocells. We will use short peptide building blocks with aromatic and ionic side chains that are designed for self- or cross-recognition. The building blocks can dimerize through reversible or irreversible chemical bond formation, including disulfide, imine, alkene (metathesis) and peptide (native chemical ligation) bonds. Preliminary results indicate that these peptides spontaneously form coacervate droplets when dimerized. The coacervates enhance the self-replication by naturally concentrating the peptide building blocks, catalyzing the template-directed peptide dimerization and stabilizing the product. By periodic cycling of the solution temperature or pH, the coacervate protocells can be dissolved and recondensed, yielding an elementary system of self-replicating protocells. These coacervate protocells not only concentrate peptides, but also nucleotides, inorganic nanoparticles and pigments, creating a potent microreactor for prebiotic chemistry. Developing these model system will provide valuable insights in new prebiotically plausible pathways to self-replication and the origin of life.
Оригинален текст от CORDIS (на английски).
Участници
- STICHTING RADBOUD UNIVERSITEIT · NijmegenКоординаторНидерландия
Връзки
Данни: CORDIS, © Европейски съюз
