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#The assembly of peptidomimetics by multicomponent reactions (MIMICRy)

Principal investigator

Category
Projekti Hrvatske zaklade za znanost
Finance value
948.000
HRK
Start date
Sep 1st 2015
End date
Nov 30th 2019
Status
Done

Laboratory for biomimetic chemistry

#The assembly of peptidomimetics by multicomponent reactions (MIMICRy)
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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.

Publications:

1.     A. Jakas, A. Višnjevac, I. Jerić, Multicomponent approach to homo- and hetero-multivalent glycomimetics bearing rare monosaccharides. J. Org. Chem. 2020, doi: doi: 10.1021/acs.joc.9b03401

2.      K. Vlahoviček-Kahlina, J. Suć Sajko, I. Jerić (2019) C-Linked Glycomimetic Libraries Accessed by the Passerini Reaction. Int. J. Mol. Sci., 20, 6236.

3.      J. Suć Sajko, V. Ljoljić Bilić, I. Kosalec, I. Jerić, Multicomponent Approach to a Library of N‑Substituted γ‑Lactams. ACS Comb. Sci. 2019, 21, 28−34.

4.      K. Vazdar, I. Jerić, Amino-b-lactams in Ugi reaction: An efficient method for preparation of functionalized peptidomimetics. Tetrahedron 74 (2018) 7495e7506

5.      K. Vlahoviček-Kahlina, M. Vazdar, A. Jakas, V. Smrečki, I. Jerić, J. Org. Chem. 2018, 83, 13146-13156.

6.      L. Brkljačić, I. Jerić, Glutamic acid‐related hydrazine reagent for the derivatization of carbonyl compounds. J. Mass Spectrom. 2018;53:649–654

7.      M. Glavaš, M. Gredičak, I. Jerić, (2018) Enediyne-Comprising Amino Aldehydes in the Passerini Reaction. ACS Comb. Sci. 20 (2018) 151 -155

8.      J. Suć, D. Barić, I. Jerić (2016) Multicomponent synthesis of hydrazino depsipeptidesRSC Adv. 6 99664-99675

9.   J. Suć, L.-M. Tumir, Lj. Glavaš-Obrovac, M. Jukić, I. Piantanida* and I. Jerić, Impact of α-hydrazino acids embedded in short fluorescent peptides on peptide interaction with DNA and RNA. Org. Biomol. Chem. 14 (2016) 4865–4874.

Other associates

Lidija Varga-Defterdarović

Andreja Jakas

Matija Gredičak

Katarina Vazdar

Kristina Vlahoviček-Kahlina

Josipa Suć Sajko

Lidija Brkljačić

Lidija-Marija Tumir

Ivana Kovačić

Mateja Matišić

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