H2020Обмен на изследователи2016–2019

PELICO · Peptidomimetics with photocontrolled biological activity

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

Период: 2016-01-01 → 2019-12-31
Финансиране от ЕС: 688 500 €
Участници: 4
Схема: MSCA-RISE

Линиите свързват координатора с партньорите.

Накратко на български

Циклични пептидни аналоги се модифицират с фотопревключватели, за да се активират или деактивират чрез светлина. Това помага за намаляване на токсичността на лекарствата, като тяхното действие се насочва точно към мястото на увреждането в тялото.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Peptidomimetics with photocontrolled biological activity

One of the main problems in pharmacology is low success rate of drug candidates in clinical trials. Despite enormous resources spent on the research and discovery of investigational drugs, especially for treatment of cancer, they still have very low success rate. The drug candidates fail mostly because of their excess toxicity. The project addressed the problem by discovering light-controllable drug candidates, the biological activity of which can be deactivated (“switched off”) or activated (“switched on”) by non-ionisable light irradiation. The light-controllable drugs can be administered in the inactive, non-toxic form, and then activated by light only when and where required for treatment. The activation by light can be done with very high spatiotemporal precision in the lesion site, leaving the rest of the patient body unaffected. Consequently, the light-controllable drugs will have favourable pharmacological characteristics, such as high selectivity of therapeutic action, reduced overall side-toxicity and significantly augmented safety that will increase their success rate in clinical trials. As the result, the healthcare industry will obtain a new treatment modality to address unmet medical needs in Europe and in the whole world. The main objective of the Project was the design, synthesis, as well as detailed structural and functional studies of cyclic peptide analogues (peptidomimetics), whose biological activity could be effectively controlled by light. The idea behind the design of such compounds relies on the modification of the known biologically active cyclic peptides by using photoisomerizable (photoswitchable) building blocks to get photocontrolled peptidomimetics. The modified peptides can change their structure upon irradiation with light of different wavelengths (Fig. 1), so their properties can be controlled by light. Consortium members have explored and patented the design principles which allow obtaining practically applicable photocontrolled peptidomimetics.

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

Цел на проекта

The expertise, resources and specific knowledge of all participating parties will be combined to achieve a breakthrough in design, synthesis and application of peptide analogues (peptidomimetics) possessing photo-controlled biological activities, with special emphasis on anti-microbial and anti-cancer activities. The main idea behind the Project consists in chemical incorporation of artificial photo-controllable building blocks into known biologically active peptides by replacing their natural building blocks – the amino acid residues. Such a modification would provide photocontrolled peptidomimetics which can reversibly change their structure between two different photo-forms upon irradiation with light of different wavelength. The participating parties possess general know-how for design of the peptidomimetics which can exist in two photo-forms, biologically active and inactive ones, reversibly interconvertible by light of different wavelength. This opens a possibility to convert inactive peptidomimetics to active compounds by irradiation with physiologically benign light directly in tissues with very high spatiotemporal precision and can be a fundamental basis of new therapeutic strategies. The research staff exchange and other activities planned under the Project will be dedicated to accomplish four complementary work packages: (i) carrying out pharmacokinetic and toxicity studies of the photocontrolled peptidomimetics synthesized by the parties previously; (ii) evaluation of novel photocontrolled building block chemotypes for their compatibility with peptides; (iii) creation of new photocontrolled peptidomimetics, especially based on the novel building blocks and the know-how developed by the parties (e.g. using “stapled peptides” technology); (iv) multidisciplinary training of the researchers whose future work will be aimed at further development of the most advanced photocontrolled peptidomimetics as drugs suitable for photodynamic therapy.

Оригинален текст от CORDIS (на английски).

Участници

ENAMINE LIMITED LIABILITY COMPANY,RESEARCH AND PRODUCTION ENTERPRISE · KYIVКоординаторУкрайна
KARLSRUHER INSTITUT FUER TECHNOLOGIE · KarlsruheГермания
LATVIJAS ORGANISKAS SINTEZES INSTITUTS · RigaЛатвия
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEОбединеното кралство