Nucleic Acid Aptamers Emerging as Modulators of G-Protein-Coupled Receptors: Challenge to Difficult Cell Surface Proteins

Abstract

G-protein-coupled receptors (GPCRs), among various cell surface proteins, are essential targets in the fields of basic science and drug discovery. The discovery and development of modulators for the receptors have provided deep insights into the mechanism of action of receptors and have led to a new therapeutic option for human diseases. Although various modulators against GPCRs have been developed to date, the identification of new modulators for GPCRs remains a challenge due to several technical problems and limitations. To overcome this situation, a variety of strategies have been developed by several modalities, including nucleic acid aptamers, which are emerging as unique molecules isolated by a repetitive selection process against various types of targets from an enormous combinatorial library. This review summarized the achievements in the development of aptamers targeting GPCRs, and discussed their isolation methods and the diverse functional features of aptamers against GPCRs.

Electrostatic Impact of Brefeldin A on Thiocyanate Probes Surrounding the Interface of Arf1-BFA-ARNO4M, a Protein–Drug–Protein Complex

“…Recent success with this approach has been achieved using covalent attachments such as AMG 510 for oncogenic G12C-KRas, but this strategy depends on the availability of a reactive cysteine and can result in off-target attachment . Other strategies have largely included using peptides, proteomimetics, − nucleic acid aptamers, and antibodies; each of these methods carry their own set of benefits and drawbacks, and successful drug design has been rare. , There is a clear need for a greater understanding of how electrostatic complementarity combines with structural details to create protein–protein interfaces and how small molecules could interrupt those interactions in desired ways. To design a small molecule with the orthosteric, noncovalent binding found in most traditional drugs, a significantly better understanding of the complicated networks of electrostatic interactions between all charges and partial charges at these interfaces is clearly needed.…”