Marcin Drag

Summary

Affiliation: The Burnham Institute
Country: USA

Publications

  1. pmc Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)
    Marcin Drag
    Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 415:367-75. 2008
  2. pmc Aminopeptidase fingerprints, an integrated approach for identification of good substrates and optimal inhibitors
    Marcin Drag
    Apoptosis and Cell Death Research Program, The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 285:3310-8. 2010
  3. doi DeSUMOylating enzymes--SENPs
    Marcin Drag
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    IUBMB Life 60:734-42. 2008
  4. ncbi Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family
    Marcin Drag
    Apoptosis and Cell Death Research Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 409:461-9. 2008
  5. ncbi Novel hydroxamic acid-related phosphinates: inhibition of neutral aminopeptidase N (APN)
    Marcin Drag
    Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wroclaw, Poland
    Bioorg Med Chem Lett 17:1516-9. 2007
  6. pmc Design of ultrasensitive probes for human neutrophil elastase through hybrid combinatorial substrate library profiling
    Paulina Kasperkiewicz
    Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw 50 370, Poland
    Proc Natl Acad Sci U S A 111:2518-23. 2014
  7. ncbi Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs
    Jowita Mikolajczyk
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 282:26217-24. 2007
  8. pmc An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling, inhibitory studies and molecular modeling
    Ewelina Węglarz-Tomczak
    Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wrocław, Poland
    Biochimie 95:419-28. 2013
  9. pmc Mechanism and specificity of the human paracaspase MALT1
    Janna Hachmann
    Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Biochem J 443:287-95. 2012
  10. pmc FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity
    Cristina Pop
    Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Biochem J 433:447-57. 2011

Collaborators

Detail Information

Publications30

  1. pmc Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)
    Marcin Drag
    Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 415:367-75. 2008
    ..Together, our results reveal the importance of the dual features of (1) substrate specificity and (2) the mechanism of ubiquitin binding in determining deubiquitination by this group of proteases...
  2. pmc Aminopeptidase fingerprints, an integrated approach for identification of good substrates and optimal inhibitors
    Marcin Drag
    Apoptosis and Cell Death Research Program, The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 285:3310-8. 2010
    ....
  3. doi DeSUMOylating enzymes--SENPs
    Marcin Drag
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    IUBMB Life 60:734-42. 2008
    ..We discuss recent progress on the human SENPs and their substrates...
  4. ncbi Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family
    Marcin Drag
    Apoptosis and Cell Death Research Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 409:461-9. 2008
    ..We also show that SENP6 and 7 have an unexpected specificity that distinguishes them from other members of the family, implying that, in contrast to previous predictions, their natural substrate(s) may not be SUMO conjugates...
  5. ncbi Novel hydroxamic acid-related phosphinates: inhibition of neutral aminopeptidase N (APN)
    Marcin Drag
    Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wroclaw, Poland
    Bioorg Med Chem Lett 17:1516-9. 2007
    ..These compounds, even as racemic mixtures, are good inhibitors of APN and show strong structure activity relationship (SAR) depending on the substituents in P1 and P1' positions...
  6. pmc Design of ultrasensitive probes for human neutrophil elastase through hybrid combinatorial substrate library profiling
    Paulina Kasperkiewicz
    Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw 50 370, Poland
    Proc Natl Acad Sci U S A 111:2518-23. 2014
    ..We propose that this approach can be successfully used for any type of endopeptidase to deliver high activity and selectivity in substrates and probes. ..
  7. ncbi Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs
    Jowita Mikolajczyk
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 282:26217-24. 2007
    ..Using these synthetic substrates we reveal that the SUMO domain enhances catalysis of SENP1, -2, -5, -6, and -7, demonstrating substrate-induced activation of SENPs by SUMOs...
  8. pmc An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling, inhibitory studies and molecular modeling
    Ewelina Węglarz-Tomczak
    Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wrocław, Poland
    Biochimie 95:419-28. 2013
    ..These studies present comprehensive characterization of interactions responsible for specific ligand binding. This knowledge provides invaluable insight into understanding of the enzyme and development of novel NmAPN inhibitors...
  9. pmc Mechanism and specificity of the human paracaspase MALT1
    Janna Hachmann
    Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Biochem J 443:287-95. 2012
    ..Thus MALT1 has many similarities to caspase 8, even cleaving the putative target protein CYLD with comparable efficiencies, but with diametrically opposite primary substrate specificity...
  10. pmc FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity
    Cristina Pop
    Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Biochem J 433:447-57. 2011
    ..Based on these results we propose a mechanism of caspase 8 activation by dimerization in the presence of FLIP(L), as well as a mechanism of caspase 8 functional divergence in apoptotic and non-apoptotic pathways...
  11. doi Toward very potent, non-covalent organophosphonate inhibitors of cathepsin C and related enzymes by 2-amino-1-hydroxy-alkanephosphonates dipeptides
    Marcin Drag
    Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, Wrocław, Poland
    Biochimie 95:1640-9. 2013
    ..These dipeptide mimetics appear also to be potent inhibitors of other cysteine proteases such as papain, cathepsin B and cathepsin K, thus providing new leading structures for these medicinally important enzymes. ..
  12. pmc Caspase substrates and inhibitors
    Marcin Poreba
    Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, 50 370 Wrocław, Poland
    Cold Spring Harb Perspect Biol 5:a008680. 2013
    ..Together, these chemical and proteomics technologies are setting the scene for designing and implementing control of caspase activity as appropriate targets for disease therapy. ..
  13. ncbi Current and prospective applications of non-proteinogenic amino acids in profiling of proteases substrate specificity
    Paulina Kasperkiewicz
    Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, 50 370 Wroclaw, Poland
    Biol Chem 393:843-51. 2012
    ..In this review, we discuss current and prospective technologies for application of non-proteinogenic amino acids in protease substrate specificity profiling...
  14. pmc Activity, specificity, and probe design for the smallpox virus protease K7L
    Alexander E Aleshin
    Program in Apoptosis and Cell Death Research, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Biol Chem 287:39470-9. 2012
    ..Our study thus provides proof-of-concept for the design of inhibitors and probes that may contribute both to a better understanding of the role of K7L in the virus life cycle and the design of novel anti-virals...
  15. pmc Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum
    Marcin Poreba
    Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, Poland
    PLoS ONE 7:e31938. 2012
    ..These exopeptidases are potential targets for the development of a new class of anti-malaria drugs...
  16. doi Identification of very potent inhibitor of human aminopeptidase N (CD13)
    Renata Grzywa
    Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego, Wroclaw, Poland
    Bioorg Med Chem Lett 20:2497-9. 2010
    ..This SAR approach yielded a very potent inhibitor of human aminopeptidase N: alpha(1)-amino-3-phenylpropyl(alpha(2)-hydroxy-3-phenylpropyl)phosphinic acid with an IC(50)=60 nM...
  17. pmc Synthetic substrates for measuring activity of autophagy proteases: autophagins (Atg4)
    Chih Wen Shu
    Sanford Burnham Medical Research Institute, Program on Apoptosis and Cell Death Research, La Jolla, CA, USA
    Autophagy 6:936-47. 2010
    ..Therefore, the synthetic substrates for autophagins reported here provide new research tools for studying autophagy...
  18. doi S1 pocket fingerprints of human and bacterial methionine aminopeptidases determined using fluorogenic libraries of substrates and phosphorus based inhibitors
    Marcin Poreba
    Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wroclaw, Poland
    Biochimie 94:704-10. 2012
    ..The substrate-derived results were verified using several phosphonate and phosphinate-based inhibitors...
  19. doi Substrate specificity screening of oat (Avena sativa) seeds aminopeptidase demonstrate unusually broad tolerance in S1 pocket
    Anna D Gajda
    Department of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wrocław, Poland
    Plant Physiol Biochem 54:6-9. 2012
    ..In the case of unnatural amino acids hydrophobic residues (hPhe and hCha) and basic hArg were preferentially recognized...
  20. pmc Activation and specificity of human caspase-10
    Katherine Wachmann
    Program in Apoptosis and Cell Death Research, Sanford BurnhamMedical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 49:8307-15. 2010
    ....
  21. doi Metallo-aminopeptidase inhibitors
    Artur Mucha
    Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wrocław, Poland
    Biochimie 92:1509-29. 2010
    ..Here, we present several approaches for the design of inhibitors for metallo-aminopeptidases. The optimized structures should be considered as potential leads in the drug discovery process against endogenous and infectious diseases...
  22. pmc Emerging principles in protease-based drug discovery
    Marcin Drag
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Nat Rev Drug Discov 9:690-701. 2010
    ....
  23. doi Positional scanning substrate combinatorial library (PS-SCL) approach to define caspase substrate specificity
    Marcin Poreba
    Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, Poland
    Methods Mol Biol 1133:41-59. 2014
    ..Additionally, we describe procedures for the identification of optimal substrates sequence after PS-SCL, solid phase synthesis, and purification of selected fluorogenic substrates, as well as their kinetic analysis. ..
  24. pmc A remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural amino acids
    Anna Byzia
    Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50 370, Wrocław, Poland
    Amino Acids 46:1313-20. 2014
    ..75 × 10(5) M(-1) s(-1)) as compared to L-Arg (1.5 × 10(3) M(-1) s(-1)). This information can be used for design of potent inhibitors of this enzyme, but may also suggest yet undiscovered functions or specificities of LTA4H...
  25. doi Comparision of the cytotoxic effects of birch bark extract, betulin and betulinic acid towards human gastric carcinoma and pancreatic carcinoma drug-sensitive and drug-resistant cell lines
    Marcin Drag
    Wroclaw University of Technology, Wybrzeze Wyspianskiego, Poland
    Molecules 14:1639-51. 2009
    ..Our results show significant differences in sensitivity between cell lines depending on the compound used, and suggest that both betulin and betulinic acid can be considered as a promising leads in the treatment of cancer...
  26. ncbi alpha-Aminoalkylphosphonates as a tool in experimental optimisation of P1 side chain shape of potential inhibitors in S1 pocket of leucine- and neutral aminopeptidases
    Marcin Drag
    Institute of Organic Chemistry, Biochemistry and Biotechnology, University of Technology, Wybrzeze Wyspianskiego 27, 50 370 Wroclaw, Poland
    Eur J Med Chem 40:764-71. 2005
    ..Additional comparison of the inhibitory activity obtained for aminopeptidase N (APN, E.C.3.4.11.2) give insight into structural preferences of both enzymes...
  27. pmc Chemical target validation studies of aminopeptidase in malaria parasites using alpha-aminoalkylphosphonate and phosphonopeptide inhibitors
    Eithne Cunningham
    Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland
    Antimicrob Agents Chemother 52:3221-8. 2008
    ..There was a strong correlation between the potencies of the compounds against whole parasites and against the enzyme, suggesting that M17 and/or M1 aminopeptidases may be valid antimalarial drug targets...
  28. ncbi Small molecules not direct activators of caspases
    Jean Bernard Denault
    Nat Chem Biol 3:519; author reply 520. 2007
  29. ncbi Stereoselective synthesis of 1-aminoalkanephosphonic acids with two chiral centers and their activity towards leucine aminopeptidase
    Marcin Drag
    Institute of Organic Chemistry, Biochemistry and Biotechnology, University of Technology, Wroclaw, Poland
    Chirality 15:S104-7. 2003
    ..They appeared to act as moderate inhibitors of kidney leucine aminopeptidase with potency dependent on the absolute configuration of both centers of chirality...
  30. ncbi Redox reaction between amino-(3,4-dihydroxyphenyl)methyl phosphonic acid and dopaquinone is responsible for the apparent inhibitory effect on tyrosinase
    Beata Gasowska
    Institute of Chemistry, University of Opole, Poland
    Eur J Biochem 269:4098-104. 2002
    ..Decomposition of the phosphonic o-quinone to 3,4-dihydroxybenzaldehyde drives the reaction against the slightly unfavorable difference in redox potentials...