Cargando…

Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics

Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the 23S rRNA at or near the peptidyl transferase center. However, their...

Descripción completa

Detalles Bibliográficos
Autores principales: Jednačak, Tomislav, Mikulandra, Ivana, Novak, Predrag
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589898/
https://www.ncbi.nlm.nih.gov/pubmed/33096889
http://dx.doi.org/10.3390/ijms21207799
_version_ 1783600685053378560
author Jednačak, Tomislav
Mikulandra, Ivana
Novak, Predrag
author_facet Jednačak, Tomislav
Mikulandra, Ivana
Novak, Predrag
author_sort Jednačak, Tomislav
collection PubMed
description Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the 23S rRNA at or near the peptidyl transferase center. However, their excellent antibacterial profile was largely compromised by the emergence of bacterial resistance. Today, fighting resistance to antibiotics is one of the greatest challenges in medicinal chemistry. Considering various physicochemical properties of macrolides, understanding their structure and interactions with macromolecular targets is crucial for the design of new antibiotics efficient against resistant pathogens. The solid-state structures of some macrolide-ribosome complexes have recently been solved, throwing new light on the macrolide binding mechanisms. On the other hand, a combination of NMR spectroscopy and molecular modeling calculations can be applied to study free and bound conformations in solution. In this article, a description of advanced physicochemical methods for elucidating the structure and interactions of macrolide antibiotics in solid state and solution will be provided, and their principal advantages and drawbacks will be discussed.
format Online
Article
Text
id pubmed-7589898
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75898982020-10-29 Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics Jednačak, Tomislav Mikulandra, Ivana Novak, Predrag Int J Mol Sci Review Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the 23S rRNA at or near the peptidyl transferase center. However, their excellent antibacterial profile was largely compromised by the emergence of bacterial resistance. Today, fighting resistance to antibiotics is one of the greatest challenges in medicinal chemistry. Considering various physicochemical properties of macrolides, understanding their structure and interactions with macromolecular targets is crucial for the design of new antibiotics efficient against resistant pathogens. The solid-state structures of some macrolide-ribosome complexes have recently been solved, throwing new light on the macrolide binding mechanisms. On the other hand, a combination of NMR spectroscopy and molecular modeling calculations can be applied to study free and bound conformations in solution. In this article, a description of advanced physicochemical methods for elucidating the structure and interactions of macrolide antibiotics in solid state and solution will be provided, and their principal advantages and drawbacks will be discussed. MDPI 2020-10-21 /pmc/articles/PMC7589898/ /pubmed/33096889 http://dx.doi.org/10.3390/ijms21207799 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Jednačak, Tomislav
Mikulandra, Ivana
Novak, Predrag
Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
title Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
title_full Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
title_fullStr Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
title_full_unstemmed Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
title_short Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
title_sort advanced methods for studying structure and interactions of macrolide antibiotics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589898/
https://www.ncbi.nlm.nih.gov/pubmed/33096889
http://dx.doi.org/10.3390/ijms21207799
work_keys_str_mv AT jednacaktomislav advancedmethodsforstudyingstructureandinteractionsofmacrolideantibiotics
AT mikulandraivana advancedmethodsforstudyingstructureandinteractionsofmacrolideantibiotics
AT novakpredrag advancedmethodsforstudyingstructureandinteractionsofmacrolideantibiotics