Miklos Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides

作者：Koehn Maja

来源：Journal of Peptide Science, 2017, 23(10): 749-756.

DOI：10.1002/psc.3033

• protein phosphatases
• allosteric modulation
• active site inhibition
• peptidomimetics
• macrocyclic peptides
• microcystin
• peptide-based drug design
• phosphatase database DEPOD

Protein phosphatase-1 and phosphatase-2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past. In the last decade, new approaches have been developed to overcome these hurdles and have strongly revived the field. I will focus here on peptide-based approaches, which contributed to showing that these phosphatases can be targeted selectively and aided in rethinking the design of selective phosphatase modulators. Finally, I will give a perspective on , the human dephosphorylation database, and how it can aid phosphatase modulator design.

• 出版日期2017-10