Ribosome Inhibition-related Targets

Ribosome-specific targets and the available information are powerful guides for developing more potent ribosome-associated inhibitors. Creative Biolabs is pleased to provide customers around the world with comprehensive ribosome analysis services to accelerate your research projects.

Overview of Ribosome Targets

Ribosomes are composed of two unequal subunits, both of which have several functional sites, where various catalytic and regulatory activities occur during protein synthesis. For example, small subunits are involved in decoding genetic information while the peptidyl transferase center (PTC) of the large subunit links amino acids into nascent polypeptides, which then cross the bulk of the large subunit through the nascent peptide exit channel (NPET). What is more, the ribosome has three tRNA binding sites, an aminoacyl (A) site, a peptidyl (P) site, and an export (E) site. Furthermore, both subunits possess diverse factor-binding pockets where translational regulatory activities occur that are closely related to ribosomal function. In conclusion, the structure of the ribosome is very complex, containing binding sites for mRNA, tRNA, and ribosomal factors. Modification of the ribosome by inhibitory ligands can interfere with ribosomal function.

Ribosome Inhibition Targets

Ribosomes are indispensable machinery for protein synthesis in cells. Compared to normal cells, ribosome synthesis is increased in cancer cells to maintain unrestricted growth. In recent years, ribosome biosynthesis has emerged as an attractive target for cancer therapy, and some compounds that inhibit ribosome production have entered clinical trials. In addition, scientists have found that many cancer therapeutics exert their inhibitory effect on ribosome biosynthesis by specifically interfering with rRNA synthesis or pre-rRNA processing.

Ribosome Inhibition Targets for Drug Development

Ribosomes are one of the main targets of many antibiotics in cells. They function by binding to various functional centers to lock the ribosome in a specific conformation. For instance, two classical antibiotics, chloramphenicol and erythromycin, compete for binding to the PTC and NPET sites of bacterial ribosomes. It is worth noting that PTC and NPET are the target sites for many different inhibitors, including macrolides, phenols, and ketolides. Moreover, several naturally occurring potent antibiotics, such as protomycin, have been discovered with distinct targets on the large subunit. Additionally, several compounds such as protomethycin have been identified that appear to target novel sites on the 30S subunit. This evidence provides new directions for the development of new ribosome-targeted inhibitors.

Fig. 1 Effects of ribosome inhibition in various cancer models.¹

Clearly, an understanding of ribosomal targets and molecular mechanisms is critical for drug development. As a leader in ribosome services, Creative Biolabs specializes in providing customers with customized ribosome analysis services. Please contact us for more details.

Reference

1. Gilles, Arnaud, et al. "Targeting the human 80S ribosome in cancer: from structure to function and drug design for innovative adjuvant therapeutic strategies." Cells 9.3 (2020): 629.