Utilization of Biased G Protein-Coupled Receptor Signaling towards Development of Safer and Personalized Therapeutics

Molecules

卷:24

Samman Mansoor¹  Metehan Ilter²  Ozge Sensoy³ 

[1] Department of Biomedical Engineering and Bioinformatics, The Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, Istanbul 34810, Turkey;

[2] Department of Biomedical Engineering, The School of Engineering and Natural Sciences, Istanbul Medipol University, Istanbul 34810, Turkey;

[3] Department of Computer Engineering, The School of Engineering and Natural Sciences, Istanbul Medipol University, Istanbul 34810, Turkey;

关键词: GPCR;    biased signaling;    allostery;    personalized medicine;    functional selectivity;    oligomerization;    single nucleotide polymorphism;    arresin;    G protein;   

DOI  :  10.3390/molecules24112052

来源: DOAJ

【 摘 要 】

G protein-coupled receptors (GPCRs) are involved in a wide variety of physiological processes. Therefore, approximately 40% of currently prescribed drugs have targeted this receptor family. Discovery of $\beta$ -arrestin mediated signaling and also separability of G protein and $\beta$ -arrestin signaling pathways have switched the research focus in the GPCR field towards development of biased ligands, which provide engagement of the receptor with a certain effector, thus enriching a specific signaling pathway. In this review, we summarize possible factors that impact signaling profiles of GPCRs such as oligomerization, drug treatment, disease conditions, genetic background, etc. along with relevant molecules that can be used to modulate signaling properties of GPCRs such as allosteric or bitopic ligands, ions, aptamers and pepducins. Moreover, we also discuss the importance of inclusion of pharmacogenomics and molecular dynamics simulations to achieve a holistic understanding of the relation between genetic background and structure and function of GPCRs and GPCR-related proteins. Consequently, specific downstream signaling pathways can be enriched while those that bring unwanted side effects can be prevented on a patient-specific basis. This will improve studies that centered on development of safer and personalized therapeutics, thus alleviating the burden on economy and public health.

【 授权许可】

Unknown