Cleavable molecular nanocarrier:antimetabolite conjugates of antimicrobial activity

This project contains proposal of execution of complex, interdisciplinary studies concerning rational design, synthesis and determination of biological properties of conjugates of molecular nanocarriers with inhibitors of bacterial and fungal enzymes (antimetabolites), containing in their structures linkers cleavable by enzymes present in microbial cells but stable in blood serum. Components of the conjugates will be as follows: cell penetrating peptides, molecular umbrellas and lipidic molecules as molecular nanocarriers, linkers cleavable by esterases and β-glycosidases and inter alia, 5-fluorocytosine and inhibitors of bacterial alanine racemase as antimetabolites. The main goal of the proposed studies is verification of reality and applicability of a novel concept of construction of potential antifungal and antibacterial drugs based on conjugation of effective molecular nanocarriers with antimetabolites through the linkers selectively cleaved in microbial cells. Expected results include: determination of molecular basis and factors determining biological activity of novel conjugates and formulation of guidelines for further optimization of conjugate structures in terms of their penetrability through biological membranes, stability in blood serum and selective toxicity.

Details

Financial Program Name:

OPUS

Organization:

Narodowe Centrum Nauki (NCN) (National Science Centre)

Agreement:

UMO-2020/39/B/ST4/01509 z dnia 2021-06-08

Realisation period:

2021-06-08 - 2024-06-07

Project manager:

prof. dr hab. inż. Sławomir Milewski

Team members:

investigator dr inż. Andrzej Stanisław Skwarecki

Realised in:

Department of Pharmaceutical Technology and Biochemistry

Project's value:

1 378 400.00 PLN

Request type:

National Research Programmes

Domestic:

Domestic project

Verified by:

Gdańsk University of Technology

Papers associated with that project

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total: 2

Year 2023

Fatty acids as molecular carriers in cleavable antifungal conjugates
Publication
- EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY - Year 2023
Conjugates composed of C2-18 fatty acid (FA) residues as a molecular carrier and 5-fluorocytosine (5-FC) as an active agent, released upon the action of intracellular esterases on the ester bond between FA and “trimethyl lock” intramolecular linker, demonstrate good in vitro activity against human pathogenic yeasts of Candida spp. The minimal inhibitory concentrations (MIC) values for the most active conjugates containing caprylic...

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Year 2021

Amino Acid Based Antimicrobial Agents – Synthesis and Properties
Publication
- CHEMMEDCHEM - Year 2021
Structures of several dozen of known antibacterial, antifungal or antiprotozoal agents are based on the amino acid scaffold. In most of them, the amino acid skeleton is of a crucial importance for their antimicrobial activity, since very often they are structural analogs of amino acid intermediates of different microbial biosynthetic pathways. Particularly, some aminophosphonate or aminoboronate analogs of protein amino acids are...

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