The assembly of peptidomimetics by multicomponent reactions (MIMICRy)

Datum početka projekta
01.09.2015.
Datum kraja projekta
31.08.2019.
Status
Aktivan
Kategorija projekta
Projekti Hrvatske zaklade za znanost
Ugovoreni iznos financiranja
948.000 HRK

Screening of small-molecule libraries has been the most commonly used tool in drug discovery over the past two decades. However, currently used libraries lack diversity in terms of biological and chemical properties, i.e. “chemical space” covered is infinitely small. In the past 15 years, only 15 % of the emerging novel chemical entities have been novel classes of compounds. This limitation significantly hampers development of novel lead compounds needed to tackle new generations of biological targets.

The project goal is to expand the chemical space of natural product-like compounds by using multicomponent reactions. This will be achieved by: (a) developing novel non-natural amino acid-, carbohydrate- and enediyne-based building blocks; (b) performing Passerini and Ugi multicomponent reactions to obtain structurally diverse linear and macrocyclic compounds and (c) studying the stereochemistry of multicomponent reactions.

Project results, and the knowledge about methodologies and stereochemistry of novel compounds, are highly relevant for the following fields: medicinal chemistry - novel structures to fill the libraries; catalyst development – particularly enediyne-based macrocycles; and biomedical studies – carbohydrate-based compounds can be used as biological probes. Project is aligned with the goal of the Croatian Science Foundation: development of competitive research environment, and creation of new knowledge for the strengthening the Croatian economy.

Project results will be the base for the generation of libraries with structurally diverse peptide-like small molecules and macrocyclic compounds, as an answer to the pharmaceutical industry needs: identification of yet undisclosed biological targets and the development of novel lead compounds. Therefore, project contributes to one of the key objectives in the European Union: improving the health of EU citizens for generation of wealth and public wellbeing. 

Glavni istraživač / voditelj
Ivanka Jerić

Ivanka Jerić, dr. sc.

znanstvena savjetnica +385 1 456 0980

Ostali suradnici

Lidija Varga-Defterdarović

Andreja Jakas

Matija Gredičak

Katarina Vazdar

Kristina Vlahoviček-Kahlina

Josipa Suć

Lidija Brkljačić

Lidija-Marija Tumir

Napomena

The project aims to expand the chemical space of peptide-like compounds by using non-natural amino acid-, carbohydrate-, and enediyne-derived building blocks in the Passerini and Ugi multicomponent reactions.

This will be achieved by:

  1. The development of building blocks based on non-natural amino acids, carbohydrates and enediynes
  2. The utilization of developed building blocks in Passerini and Ugi reactions
  3. Performing Passerini and Ugi multicomponent reactions with bifunctional building blocks to obtain macrocyclic products
  4. Studying the effect of novel building blocks on the stereochemical outcome of the reactions

Long-term ambition of this project is generation of libraries with peptide-like small molecules and macrocyclic compounds. Libraries will be designed for screening against biomolecules (nucleic acids, proteins) or designed as receptors or catalysts.