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 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.

How will the identification and therapeutic intervention of genetic targets in oncology evolve for future therapy?

INTRODUCTION: Mapping of the human genome, together with the broad understanding of new biomolecular pathways involved in cancer development, represents a huge dividing line for advances in cancer treatment. This special article aims to express the next evolution of cancer therapy, while also considering the challenges and uncertainties facing future directions. AREA COVERED: The recent achievements of medical science in the oncology field concern both new diagnostic techniques, such as liquid biopsy, and therapeutic strategies with innovative anticancer drugs. Although several molecular characteristics of tumors are linked to the tissue of origin, some mutations are shared by multiple tumor histologies, thus paving the way for what is called 'precision oncology.' The article highlights the importance of identifying new mutations and biomolecular pathways that can be pursued with new anticancer drugs. EXPERT OPINION: Oncology and medical science have made great progress in understanding new molecular targets; being able to early identify tumor markers that are not confined to a single organ through minimally invasive diagnostic techniques allows us to design new effective therapeutic strategies. Multidisciplinary teams now aim to evaluate the most appropriate and personalized diagnostic/therapeutic approach for the individual patient.