Earticle

초록

영어

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. The application of structure-based in-silico methods to drug discovery is still considered a major challenge, especially when the x-ray structure of the target protein is unknown. Such is the case with human CCR2 and CCR5, the most important members of the chemokine receptor family and also a potential drug target. Herein, we review the success stories of combined receptor modeling/mutagenesis approach to probe the allosteric nature of chemokine receptor binding by small molecule antagonists for CCR2 and CCR5 using Rhodopsin as template. We also urged the importance of recently available β2-andrenergic receptor as an alternate template to guide mutagenesis. The results demonstrate the usefulness and robustness of in-silico 3D models. These models could also be useful for the design of novel and potent CCR2 and CCR5 antagonists using structure based drug design.

목차

Abstract
 1. Introduction
 2. Experimental Section
  2.1. Homology Modeling of CCR2 and CCR5
  2.2. Successful Application of Rhodopsin Based CCR2 Models
  2.3. Successful Application of Rhodopsin Based CCR5 Models
  2.4. Allosteric Binding of CCR2 and CCR5 Antagonists
  2.5. Use of β2-Adrenergic Receptor Structure as an Alternative Template
 3. Conclusion
 References

키워드

저자

• Gugan Kothandan [ Department of Bio-New Drug Development, College of Medicine, Chosun University ]
• Seung Joo Cho [ Department of Cellular ·Molecular Medicine and Research Center for Resistant Cells, College of Medicine, Chosun University ] Corresponding Author

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  통합자연과학논문집(구 조선자연과학논문집) [Journal of Integrative Natural Science]

• 간기

  계간

• pISSN

  2005-1042

• 수록기간

  2008~2025

• 등재여부

  KCI 등재

• 십진분류

  KDC 405 DDC 505