1. Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library

Amy Emery, Bryn S. Hardwick, Alex T. Crooks, Nadia Milech, Paul M. Watt, Chandan Mithra, Vikrant Kumar, Saranya Giridharan, Gayathri Sadasivam, Subashini Mathivanan, Sneha Sudhakar, Sneha Bairy, Kavitha Bharatham, Manjunath A. Hurakadli, Thazhe K. Prasad, Neelagandan Kamariah, Markus Muellner, Miguel Coelho, Christopher J. Torrance, Grahame J. McKenzie, and Ashok R. Venkitaraman

                    Cell Chemical Biology 28, 1–14, November 18, 2021

               Highlights

  • We describe protein interference, an approach to identify and validate new drug targets
  • A genetic screen identifies a protein interference probe inducing FOXO3a reactivation
  • The probe defines a druggable binding site in the 14-3-3 signal regulator family
  • We illustrate a workflow to parse complex cellular pathway for new drug targets

                 Full Article: https://www.cell.com/cell-chemical-biology/pdfExtended/S2451-9456(21)00254-3

  1. Targeting Phosphopeptide Recognition by the Human BRCA1 Tandem BRCT Domain to Interrupt BRCA1-Dependent Signaling

Periasamy J, Kurdekar V, Jasti S, Nijaguna MB, Boggaram S, Hurakadli MA, Raina D, Kurup LM, Chintha C,Manjunath K, Goyal A, Sadasivam G, Bharatham K, Padigaru M, Potluri V, Venkitaraman AR

                 Cell Chemical Biology 25, 1–14, June 21, 2018

 

Highlights

  • Bractoppin selectively blocks phosphopeptide recognition by the BRCA1 tBRCT domain

  • Bractoppin engages tBRCT residues recognizing pSer, plus an adjacent pocket

  • Bractoppin interrupts BRCA1 tBRCT-dependent cellular signals evoked by DNA damage

  • This work opens avenues to inhibit intracellular signaling by the tBRCT domain famil

 

Full article:

https://www.ncbi.nlm.nih.gov/pubmed/29606576

 

 

 

  1. Structure-Guided Synthesis and Evaluation of Small-Molecule Inhibitors Targeting Protein-Protein Interactions of BRCA1 tBRCT Domain

Kurdekar V, Giridharan S, Subbarao J, Nijaguna MB, Periasamy J, Boggaram S, Shivange AV, Sadasivam G, Padigaru M, Potluri V, Venkitaraman AR, Bharatham K

ChemMedChem. 2019 Sep 18;14(18):1620-1632

Full Article: https://www.ncbi.nlm.nih.gov/pubmed/31334915