New Acyloxymethyl Ketones: Useful Probes for Cysteine Protease Profiling

Anca G. Coman; Codruta C. Paraschivescu; Niculina D. Hadade; Andrei Juncu; Ovidiu Vlaicu; Costin-Ioan Popescu; Mihaela Matache

doi:10.1055/s-0035-1562781

Synthesis, Table of Contents

Synthesis 2016; 48(22): 3917-3923
DOI: 10.1055/s-0035-1562781

paper

New Acyloxymethyl Ketones: Useful Probes for Cysteine Protease Profiling

Anca G. Coman

^aUniversity of Bucharest, Faculty of Chemistry, Department of Organic Chemistry, Biochemistry and Catalysis, 90 Panduri Street, 050663 Bucharest, Romania Email: mihaela.matache@g.unibuc.ro

,

Codruta C. Paraschivescu

^aUniversity of Bucharest, Faculty of Chemistry, Department of Organic Chemistry, Biochemistry and Catalysis, 90 Panduri Street, 050663 Bucharest, Romania Email: mihaela.matache@g.unibuc.ro

,

Niculina D. Hadade

^bFaculty of Chemistry and Chemical Engineering, ‘Babeș-Bolyai’ University, 11 Arany Janos Str., 400028 Cluj-Napoca, Romania

,

Andrei Juncu

^cInstitute of Biochemistry of the Romanian Academy, 296 Splaiul Independetei Avenue, 060031 Bucharest, Romania

,

Ovidiu Vlaicu

^cInstitute of Biochemistry of the Romanian Academy, 296 Splaiul Independetei Avenue, 060031 Bucharest, Romania

,

Costin-Ioan Popescu

^cInstitute of Biochemistry of the Romanian Academy, 296 Splaiul Independetei Avenue, 060031 Bucharest, Romania

,

Mihaela Matache*

^aUniversity of Bucharest, Faculty of Chemistry, Department of Organic Chemistry, Biochemistry and Catalysis, 90 Panduri Street, 050663 Bucharest, Romania Email: mihaela.matache@g.unibuc.ro

› Author Affiliations

Abstract

All articles of this category

^§ These authors contributed equally to this work

Abstract

Peptidyl-acyloxymethyl ketones (AOMKs) belong to a class of selective, irreversible inhibitors (activity-based probes) widely used as chemical tools of investigating proteins, for example, in activity-based protein profiling. The synthesis of the AOMKs has always been challenging and current methodologies involve both solution and solid-phase synthesis. Herein, the synthesis of a new scaffold useful for the preparation of peptidyl-AOMKs is reported and it is demonstrated that the new synthetic probes bearing a 4-functionalized 2,6-dimethylbenzoate efficiently inhibit cysteine proteases like cathepsin B.

Key words

acyloxymethyl ketones - activity-based probes - peptidyl-AOMKs - 2,6-dimethylbenzoates - solid-phase peptide synthesis

Full Text

References

References

For recent reviews, see:

1a Yang P, Liu K. ChemBioChem 2015; 16: 712
1b Cravatt BF, Wright AT, Kozarich JW. Annu. Rev. Biochem. 2008; 77: 383
1c Puri AW, Bogyo M. Biochemistry 2013; 52: 5985
1d Nomura DK, Dix MM, Cravatt BF. Nat. Rev. Cancer 2010; 10: 630
1e Edgington LE, Verdoes M, Bogyo M. Curr. Opin. Chem. Biol. 2011; 15: 798

For reviews, see:

2a Otto H.-H, Schirmeister T. Chem. Rev. 1997; 97: 133
2b Powers JC, Asgian JL, Ekici OD, James KE. Chem. Rev. 2002; 102: 4639
2c Evans MJ, Cravatt BF. Chem. Rev. 2006; 106: 3279

For recent examples of applications of peptidyl-AOMKs, see:

3a Edgington LE, Verdoes M, Ortega A, Withana NP, Lee J, Syed S, Bachmann MH, Blum G, Bogyo M. J. Am. Chem. Soc. 2013; 135: 174
3b Puri AW, Lupardus PJ, Deu E, Albrow VE, Garcia KC, Bogyo M, Shen A. Chem. Biol. 2010; 17: 1201
3c Edgington LE, van Raam BJ, Verdoes M, Wierschem C, Salvesen GS, Bogyo M. Chem. Biol. 2012; 19: 340
3d Torkar A, Lenarci B, Lah T, Dive V, Devel L. Bioorg. Med. Chem. Lett. 2013; 23: 2968
3e Paulick MG, Bogyo M. ACS Chem. Biol. 2011; 6: 563
3f Lee J, Bogyo M. ACS Chem. Biol. 2010; 5: 233
3g Chong C.-M, Gao S, Chiang B.-Y, Hsu W.-H, Lin T.-C, Chen T.-C, Lin C.-H. ChemBioChem 2011; 12: 2306
3h Dechert A.-MR, MacNamara JP, Breevoort SR, Hildebrandt ER, Hembree NW, Rea AC, McLain DE, Porter SB, Schmidt WK, Dore TM. Bioorg. Med. Chem. 2010; 18: 6230
3i Henzing AJ, Dodson H, Reid JM, Kaufmann SH, Baxter RL, Earnshaw WC. J. Med. Chem. 2006; 49: 7636
3j Blum G, Mullins SR, Keren K, Fonovic M, Jedeszko C, Rice MJ, Sloane BF, Bogyo M. Nat. Chem. Biol. 2005; 1: 203
3k Kato D, Boatright KM, Berger AB, Nazif T, Blum G, Ryan C, Chehade KA. H, Salvesen GS, Bogyo M. Nat. Chem. Biol. 2005; 1: 33
3l Edem PE, Czorny S, Valliant JF. J. Med. Chem. 2014; 57: 9564

4a Krantz A, Copp L, Coles P, Smith R, Heard S. Biochemistry 1991; 30: 4678
4b Pliura DH, Bonaventura BJ, Smith RA, Coles PJ, Krantz A. Biochem. J. 1992; 288: 759

5 Mujica MT, Jung G. Synlett 1999; 1933
6 Lee A, Huang L, Ellman JA. J. Am. Chem. Soc. 1999; 121: 9907
7 Turk V, Turk B, Turk D. EMBO J. 2001; 20: 4629
8 Getman DP, Periana RA, Riley DP. US Patent 4879398, 1989
9 Coppola GM, Gong Y. Org. Prep. Proced. Int. 2007; 39: 199
10 Schou SC. J. Labelled Compd. Radiopharm. 2009; 52: 173
11 Travis BR, Sivakumar M, Hollist GO, Borhan B. Org. Lett. 2003; 5: 1031

12a Roiban G.-D, Matache M, Hădade ND, Funeriu DP. Org. Biomol. Chem. 2012; 10: 4516
12b Dobrotă C, Fasci D, Hădade ND, Roiban G.-D, Pop C, Meier VM, Dumitru I, Matache M, Salvesen GS, Funeriu D.-P. ChemBioChem 2012; 13: 80

13a Arndt F. Org. Synth. 1935; 15: 48
13b Arndt F. Org. Synth. Coll. Vol. 2 . Wiley; New York: 1943: 461

Supplementary Material

Supporting Information