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Probing Structure–Function Relationships of Serine Hydrolases and Proteases with Carbamate and Thiocarbamate Inhibitors

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Benzene-1,3-di-N-n-octylcarbamate (1), benzene-1-hydroxyl-3-N-n-octylcarbamate (2), benzene-1,3-di-N-n-ocztylthiocarbamate (3), and benzene-1-hydroxyl-3-N-n-octylthiocarbamate (4) are synthesized from 1,3-benzene-diol and are characterized as the pseudo-substrate inhibitors of acetylcholinesterase, butyrylcholinesterase, cholesterol esterase, lipase, trypsin, and chymotrypsin. For these six enzyme inhibitions by 1–4, the pK i values are linearly correlated with their log k i values – Brønsted plots. Therefore, 1–4 inhibit these enzymes through a common mechanism. Moreover, both pK i and log k i values for the inhibitions by 1,3, and 4 are linearly correlated with both pK i and log k i values for the inhibitions by 2, respectively. Thus, the pK i values for the inhibitions by 2 are defined as the nucleophilicity constants of these enzymes (nenzyme). The log k2 values for the inhibitions by 1–4 are also linearly correlated with the nenzyme values. Therefore, the nucleophilicity for serine hydrolases and proteases toward 1–4 also applies the Swain–Scott correlations.

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Abbreviations

AChE:

acetylcholinesterase

BChE:

butyrylcholinesterase

CEase:

cholesterol esterase

CT:

α-chymotrypsin

LFER:

linear free energy relationship

n enzyme :

the enzyme nucleophilicity constant

PCL:

Pseudomonas cepacia lipase

PSL:

Pseudomonas species lipase

QSAR:

quantitative structure activity relationship

QSFR:

quantitative structure function relationship

References

  • P. Bar-on C. B. Millard M. Harel H. Dvir A. Enz J. L. Sussman I. Silman (2002) Biochemistry 41 3555–3564 Occurrence Handle1:CAS:528:DC%2BD38Xht1Gktr8%3D Occurrence Handle10.1021/bi020016x

    Article  CAS  Google Scholar 

  • C. Bartolucci E. Perola L. Cellai M. Brufani D. Lamba (1999) Biochemistry 38 5714–5719 Occurrence Handle1:CAS:528:DyaK1MXitlCmtbc%3D Occurrence Handle10.1021/bi982723p

    Article  CAS  Google Scholar 

  • J. C.-H. Chen L. J. W. Miercke J. Krucinski J. R. Starr G. Saenz X. Wang C. A. Spillburg L. G. Lange J. L. Ellsworth R. M. Stroud (1998) Biochemistry 37 5107–5117 Occurrence Handle1:CAS:528:DyaK1cXisVykt7k%3D Occurrence Handle10.1021/bi972989g

    Article  CAS  Google Scholar 

  • C. L. Ellman K. D. Courtney V. J. Andres R. M. Featherstone (1961) Biochem. Pharmacol. 7 88–95 Occurrence Handle1:CAS:528:DyaF3MXht1Gns7o%3D Occurrence Handle10.1016/0006-2952(61)90145-9

    Article  CAS  Google Scholar 

  • A. R. Fersht R. J. Leatherbarrow T. N. C. Wells (1986) Nature 322 284–286 Occurrence Handle1:CAS:528:DyaL28XkvFemu7g%3D Occurrence Handle10.1038/322284a0

    Article  CAS  Google Scholar 

  • M. Harel D. M. Quinn H. K. Nair I. Silman J. L. Sussman (1996) J. Am. Chem. Soc. 118 2340–2346 Occurrence Handle1:CAS:528:DyaK28Xht1Wntb8%3D Occurrence Handle10.1021/ja952232h

    Article  CAS  Google Scholar 

  • L. Hedstrom L. Szilagyi W. J. Rutter (1992) Science 255 1249–1253 Occurrence Handle1:CAS:528:DyaK38Xkt1ansrw%3D

    CAS  Google Scholar 

  • L. Hosie L. D. Sutton D. M. Quinn (1987) J. Biol. Chem. 262 260–264 Occurrence Handle1:CAS:528:DyaL2sXivFajtw%3D%3D

    CAS  Google Scholar 

  • N. Isaacs (1995) Physical Organic Chemistry EditionNumber2nd ed. Longman U.K

    Google Scholar 

  • A. A. Kossiakoff S. A. Spencer (1981) Biochemistry 20 6462–6474 Occurrence Handle1:CAS:528:DyaL3MXls1Clt7g%3D Occurrence Handle10.1021/bi00525a027

    Article  CAS  Google Scholar 

  • J. Kraut (1977) Ann. Rev. Biochem. 46 331–358 Occurrence Handle1:CAS:528:DyaE2sXlsVOmtb0%3D Occurrence Handle10.1146/annurev.bi.46.070177.001555

    Article  CAS  Google Scholar 

  • D. A. Lang M. L. M. Mannesse G. H. Haas ParticleDe H. M. Verheij B. W. Dijkstra (1998) Eur. J. Biochem. 254 333–340 Occurrence Handle1:CAS:528:DyaK1cXjvFens7g%3D Occurrence Handle10.1046/j.1432-1327.1998.2540333.x

    Article  CAS  Google Scholar 

  • G. Lin C.-Y. Lai (1995) Tetrahedron Lett. 36 6117–6120 Occurrence Handle1:CAS:528:DyaK2MXnslWrtrw%3D Occurrence Handle10.1016/0040-4039(95)01233-8

    Article  CAS  Google Scholar 

  • G. Lin C.-Y. Lai (1996) Tetrahedron Lett. 37 193–196 Occurrence Handle1:CAS:528:DyaK28Xkt1Oisg%3D%3D Occurrence Handle10.1016/0040-4039(95)02126-4

    Article  CAS  Google Scholar 

  • G. Lin G.-H. Chen H.-C. Ho (1998) Bioorg. Med. Chem. Lett. 8 2747–2750 Occurrence Handle1:CAS:528:DyaK1cXntFSju78%3D Occurrence Handle10.1016/S0960-894X(98)00484-3

    Article  CAS  Google Scholar 

  • G. Lin C.-Y. Lai W.-C. Liao (1999a) Bioorg. Med. Chem. 7 2683–2689 Occurrence Handle1:CAS:528:DC%2BD3cXntFCiuw%3D%3D Occurrence Handle10.1016/S0968-0896(99)00213-8

    Article  CAS  Google Scholar 

  • G. Lin C.-T. Shieh H.-C. Ho J.-Y. Chouhwang W.-Y. Lin C.-P. Lu (1999b) Biochemistry 38 9971–9981 Occurrence Handle1:CAS:528:DyaK1MXktlWjtrk%3D Occurrence Handle10.1021/bi982775e

    Article  CAS  Google Scholar 

  • G. Lin C.-Y. Lai W.-C. Liao B.-H. Kuo C.-P. Lu (2000) J. Chin. Chem. Soc. 47 489–500 Occurrence Handle1:CAS:528:DC%2BD3cXksFygsLw%3D

    CAS  Google Scholar 

  • G. Lin J.-Y. Chouhwang (2001) J. Biochem. Mol. Biol. Biophys. 5 301–308 Occurrence Handle1:CAS:528:DC%2BD3MXns1Glu7k%3D

    CAS  Google Scholar 

  • S. Loudwig Y. Nicolet P. Masson J. C. Fontecilla-camps S. Bon F. Nachon M. Goeldner (2003) ChemBioChem 4 762–767 Occurrence Handle1:CAS:528:DC%2BD3sXmtlyksrk%3D Occurrence Handle10.1002/cbic.200300571

    Article  CAS  Google Scholar 

  • T. H. Lowry K. S. Richardson (1992) Mechanism and Theory in Organic Chemistry EditionNumber3rd ed., Harper & Row New York

    Google Scholar 

  • J. March (1992) Advanced Organic Chemistry EditionNumber4th ed. John Wiley New York

    Google Scholar 

  • P. Masson M.-T. Froment S. Fort F. Ribes N. Bec C. Balny L. M. Schopfer (2002) Biochim. Biophys. Acta 1597 229–243 Occurrence Handle1:CAS:528:DC%2BD38XktFKitbw%3D

    CAS  Google Scholar 

  • M. A. Phillips R. J. Fletterick (1992) Curr. Opin. Struct. Biol. 2 713–720 Occurrence Handle1:CAS:528:DyaK38XmsVOntb4%3D Occurrence Handle10.1016/0959-440X(92)90206-M

    Article  CAS  Google Scholar 

  • D. M. Quinn (1987) Chem. Rev. 87 955–979 Occurrence Handle1:CAS:528:DyaL2sXlsV2kurs%3D Occurrence Handle10.1021/cr00081a005

    Article  CAS  Google Scholar 

  • L. Savini A. Gaeta C. Fattorusso B. Catalanotti C. Campiani L. Chiasserini C. Pellerano E. Novellino D. McKissic A. Saxena (2003) J. Med. Chem. 46 1–4 Occurrence Handle1:CAS:528:DC%2BD38Xpt1yntb8%3D Occurrence Handle10.1021/jm0255668

    Article  CAS  Google Scholar 

  • T. A. Seitz R. G. Shulman (1982) Ann. Rev. Biophys. Bioeng. 11 419–444 Occurrence Handle10.1146/annurev.bb.11.060182.002223

    Article  Google Scholar 

  • J. L. Sussman M. Harel F. Frolow C. Oefner A. Goldman L. Toker I. Silman (1991) Science 253 872–879 Occurrence Handle1:CAS:528:DyaK3MXlslyitrc%3D

    CAS  Google Scholar 

  • G. Thomas (2000) Medicinal Chemistry John Wiley New York

    Google Scholar 

  • C. Walsh (1979) Enzymatic Reaction Mechanism Freeman N. Y.

    Google Scholar 

  • X. Wang C.-S. Wang J. Tang F. Dyda X. C. Zhang (1997) Structure 5 1209–1218 Occurrence Handle1:CAS:528:DyaK2sXmslOnt7s%3D Occurrence Handle10.1016/S0969-2126(97)00271-2

    Article  CAS  Google Scholar 

  • C.-g. Zhan F. Zheng D. W. Landry (2003) J. Am. Chem. Soc. 125 2462–2474 Occurrence Handle1:CAS:528:DC%2BD3sXpvVWruw%3D%3D Occurrence Handle10.1021/ja020850+

    Article  CAS  Google Scholar 

  • Y. Zhang J. Kua J. A. McCammon (2002) J. Am. Chem. Soc. 124 10572–10577 Occurrence Handle1:CAS:528:DC%2BD38XlvFGlsbk%3D Occurrence Handle10.1021/ja020243m

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Chemistry, National Chung-Hsing University, Taichung, 402, Taiwan

    G. Lin & B. -C. Hwu

  2. Department of Neurosurgery, Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan

    S. -Y. Chiou

  3. Department of Applied Chemistry, Chung-Cheng Institute of Technology, Tahsi, Taoyuan, 335, Taiwan

    C. -W. Hsieh

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  1. G. Lin
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  2. S. -Y. Chiou
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  3. B. -C. Hwu
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  4. C. -W. Hsieh
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Correspondence to G. Lin.

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Lin, G., Chiou, S.Y., Hwu, B.C. et al. Probing Structure–Function Relationships of Serine Hydrolases and Proteases with Carbamate and Thiocarbamate Inhibitors. Protein J 25, 33–43 (2006). https://doi.org/10.1007/s10930-006-0013-5

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  • DOI: https://doi.org/10.1007/s10930-006-0013-5

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