d-Amino acid mutation of PMI as potent dual peptide inhibitors of p53-MDM2/MDMX interactions

  • Bioorg Med Chem Lett. 2017 Oct 15;27(20):4678-4681. doi: 10.1016/j.bmcl.2017.09.014.
Xiang Li  1 ,  Chao Liu  2 ,  Si Chen  2 ,  Honggang Hu  2 ,  Jiacan Su  3 ,  Yan Zou  4
Affiliations
  • 1. Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China; Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, United States.
  • 2. Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China.
  • 3. Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
  • 4. Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
PMID: 28916339 DOI: 10.1016/j.bmcl.2017.09.014
Abstract

According to the previously reported potent dual l-peptide PMI of p53-MDM2/MDMX interactions, a series of d-amino acid mutational PMI analogues, PMI-1-4, with enhanced proteolytic resistence and in vitro tumor cell inhibitory activities were reported, of which Liposome-PMI-1 showed a stronger inhibitory activity against the U87 cell lines than Nutlin-3. This d-amino acid mutation strategy may give a hand for enhancing the potential of peptide drugs.

Keywords
MDM2/MDMX; P53; PMI; Peptides; Tumor; d-Amino acid.