Structure-activity relationship study of leucinostatin A, a modulator of tumor−stroma interaction. Issue 38 (20th September 2018)

• Record Type: Journal Article
• Authors: Abe, Hikaru; Kawada, Manabu; Sakashita, Chiharu; Watanabe, Takumi; Shibasaki, Masakatsu
• Is Part Of: Tetrahedron. Volume 74:Issue 38(2018)
• Page Start: 5129
• Page End: 5137
• Publication Date: 2018-09-20
• Subjects: Leucinostatin -- Structure-activity relationship -- Tumor−Stroma interaction -- Peptide -- Anticancer agent; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.05.064
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Structure-activity relationship study of leucinostatin A, a natural nonapeptide, was performed to gain insight into the structural requirements for leucinostatin A to exhibit antiproliferative activity against DU-145 prostate cancer cells under cocultured conditions with the corresponding stromal cells. Twenty truncated peptide analogs of leucinostatin A revealed that the nonapeptide structure as a whole is essential for the biological activity. Alanine scanning demonstrated the importance of some of the amino acid components, including hydroxyleucine and the second leucine from the N-terminus. Two of the three aminoisobutyric acids could be substituted with one of the enantiomers of alanine, clearly demonstrating that each methyl group in these portions has a distinct influence on the growth-inhibitory activity. Graphical abstract: Image 1