• Ph.D, 2000, the Hebrew University of Jerusalem

• B.Sc., 1994, the Hebrew University of Jerusalem

 

 

Research Focus:

Protein-Protein Interactions (PPI) mediate most of the vital processes in cells and are involved in numerous diseases. However, it is extremely challenging to make PPI drug targets. This becomes even more difficult when the interactions involve disordered protein domains.

The research in our lab focuses on using peptides for the quantitative biophysical and structural analysis of PPI in health and disease. Based on this, we develop lead peptides that modulate PPI for therapeutic purposes. We are looking at PPI in biological systems that are affected in disease, such as cancer-related pathways.

Our research strategy is:

1. Studying the molecular mechanisms of protein-protein interactions in health, to understand how the particular biological system works at the molecular level
2. Understanding what goes wrong at the molecular level in disease
3. Developing peptide-based drugs that target protein-protein interactions to restore the biological system to its healthy conditions

We are using an interdisciplinary approach combining:

1. Peptide chemistry: developing new methods for the synthesis of peptides and modified peptides
2. Protein biochemistry: new methods for protein expression and purification
3. Biophysical and biochemical studies of structure, interactions and activity of peptides and proteins

Our specific research Topics are:

1. Interactions of apoptosis-related proteins as a basis for drug design (Katz et al., J. Biol. Chem., 2012; Rotem-Bamberger S. et al., PLoS ONE, 2013; Iosub-Amir et al., Sci. Rep., 2015; Iosub-Amir et al., Chem Sci., 2019; Mayer et al., Chem. Eur. J., 2020)
   
   (Rotem-Bamberger et al., 2013)
2. Intrinsically disordered proteins: the interplay between structured and disordered domains in proteins (Amartely et al., ChemComm, 2013; Faust et al., Chem. Comm., 2014; Reingewertz et al., Biochemistry, 2015; Amartely et al., Chem. Sci., 2016; Faust et al., Chembiochem, 2018)
   
   (Amartely et al., 2016)
3. Intrinsically disordered proteins as drug targets (Mayer et al., Chem. Eur. J., 2020)
   
   (Mayer et al., 2020)
4. Developing new synthetic methods for efficient synthesis of modified peptides such as cyclic peptides (Hayouka et al., J Biol. Chem., 2012; Chandra et al., Angew. Chem. Int. Ed., 2014; Chandra et al., Org. Biomol. Chem., 2014; Chandra et al., ChemMedChem, 2016; Mamidi et al., Front. Chem., 2020) and multiphosphorylated peptides (Mamidi et al., Org. Biomol. Chem., 2019; Grunhaus et al., Eur. J. Org. Chem., 2021)
   
   (Mamidi et al., 2019)
   ​​​​​​​
5. Developing PPI-based biosensors (Amit et al., Chem. Sci., 2015; Solomon et al., Chem. Eur. J., 2022; Joshi et al., Biosens. Bioelectron., 2022)
   
   (Joshi et al., 2022)

 

 

Selected Publications

 

1. Hayouka Z, Rosenbluh J, Levin A, Loya S, Lebendiker M, Veprintsev DB, Kotler M, Hizi A, Loyter A and Friedler A (2007) “Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium”, Proc Natl Acad Sci USA, 104(20):8316-21
2. Katz C, Benyamini H, Rotem S, Lebendiker M, Danieli T, Dines M, Bronner V, Bravman T, Rudiger S and Friedler A (2008) “Molecular Basis of the Interaction Between the Anti-Apoptotic Bcl-2 Family Proteins and the Pro-Apoptotic Protein ASPP2”, Proc Natl Acad Sci USA, 105(34):12277-82
3. Katz C, Levy-Beladev L, Rotem-Bamberger S, Rito T, Rüdiger SG and Friedler A (2011) “Studying protein-protein interactions using peptide arrays”, Chem Soc Rev, 40(5):2131-45                 
4. Chandra K, Roy TK, Shalev DE, Loyter A, Gilon C, Gerber RB and Friedler A (2014) “A Tandem In Situ Peptide Cyclization through Trifluoroacetic Acid Cleavage”, Angew Chem Int Ed Engl, 53(36):9450-5
5. Iosub-Amir A, Van Rosmalen M, Mayer G, Lebendiker M, Danieli T and Friedler A (2015) “Highly homologous proteins exert opposite biological activities by using different interaction interfaces”, Sci Rep, 5, 11629
6. Amartely H, David A, Shamir M, Lebendiker M, Izraeli S and Friedler A (2016) “Differential effects of zinc binding on structured and disordered regions in the multidomain STIL protein”, Chem Sci, 7(7), 4140-4147
7. Samarasimhareddy M, Mayer D, Metanis N, Veprintsev D, Hurevich M and Friedler A (2019) “A targeted approach for the synthesis of multi-phosphorylated peptides: a tool for studying the role of phosphorylation patterns in proteins”, Org Biomol Chem, 17(42):9284-9290
8. Iosub-Amir A, Bai F, Sohn Y, Song L, Tamir S, Marjault H, Mayer G, Karmi O, Jennings P, Mittler R, Onuchic J, Friedler A and Nechushtai R (2019) “The anti-apoptotic proteins NAF-1 and iASPP interact to drive apoptosis in cancer cells” Chem Sci, 10, 665-673
9. Mayer D, Damberger FF, Samarasimhareddy M, Feldmueller M, Vuckovic Z, Flock T, Bauer B, Mutt E, Zosel F, Allain FHT, Standfuss J, Schertler GFX, Deupi X, Sommer ME, Hurevich M, Friedler A and Veprintsev DB (2019) “Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation”, Nat Commun, 10(1):1261.
10. Mayer G, Shpilt Z, Bressler S, Marcu O, Schueler-Furman O, Tshuva EY and Friedler A (2020) “Targeting an interaction between two disordered domains using a designed peptide”, Chem Eur J, 26(45):10156
11. Joshi PN, Mervinetsky E, Solomon O, Chen YJ, Yitzchaik S and Friedler A (2022) “Electrochemical biosensors based on peptide-kinase interactions at the kinase docking site”, Biosens Bioelectron, 207:114177
12. Solomon O, Sapir H, Mervinetsky E, Chen YJ, Friedler A and Yitzchaik S (2022) “Kinase Sensing Based on Protein Interactions at the Catalytic Site”, Chem Eur J, 28(17):e202200655