Stabilizing the Pro-Apoptotic BimBH3 Helix (BimSAHB) Does Not Necessarily Enhance Affinity or Biological Activity
Citations Over TimeTop 10% of 2012 papers
Abstract
An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the pro-survival Bcl-2 proteins. We attribute this loss in affinity to disruption of a network of stabilizing intramolecular interactions present in the bound state of the native peptide. Altering this network may compromise binding affinity, as in the case of the BimBH3 stapled peptide studied here. Moreover, cells exposed to these peptides do not readily undergo apoptosis, strongly indicating that BimSAHB is not inherently cell permeable.
Related Papers
- Apoptosis of human pancreatic cancer cells induced by Triptolide(2008)
- Relationships between induction of apoptosis by CDDP in Scaber cell and apoptosis-related proteins(2003)
- [Apoptosis and cytostatic agents].(1992)
- 자궁경부 상피내종양 및 자궁경부암 조직에서 bcl-2 및 c-myc 암유전자 발현과 세포증식 및 apoptosis와의 상관관계에 관한 연구(1998)
- Identification of specific genes and pathways involved in NSAIDs-induced apoptosis of human colon cancer cells(2006)