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Volumn 120, Issue 9, 1998, Pages 2008-2017

Spiropentylacetyl-CoA, a mechanism-based inactivator of acyl-CoA dehydrogenases

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DEHYDROGENASE; ENZYME INHIBITOR; FLAVINE ADENINE NUCLEOTIDE; HYPOGLYCINE A; SPIROPENTYLACETYL COENZYME A; UNCLASSIFIED DRUG;

EID: 2642710916     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9737634     Document Type: Article
Times cited : (36)

References (76)
  • 4
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    • Bray, R. C., Engel, P. C., Mayhew, S. G., Eds.; Walter de Gruyter & Co.: Berlin, and references cited therein
    • (d) Ghisla, S. In Flavins and Flavoproteins; Bray, R. C., Engel, P. C., Mayhew, S. G., Eds.; Walter de Gruyter & Co.: Berlin, 1984; p 385 and references cited therein.
    • (1984) Flavins and Flavoproteins , pp. 385
    • Ghisla, S.1
  • 11
    • 84909798182 scopus 로고
    • Curti, B., Ronchi, S., Zanetti, G., Eds.; de Gruyter: New York
    • (b) Kim, J. J. P. In Flavins and Flavoproteins; Curti, B., Ronchi, S., Zanetti, G., Eds.; de Gruyter: New York, 1991; p 291.
    • (1991) Flavins and Flavoproteins , pp. 291
    • Kim, J.J.P.1
  • 36
    • 1842435792 scopus 로고
    • Seiler, N., Jung, M. J., Koch-Weser, J., Eds.; Elsevier-North-Holland: Amsterdam
    • (c) Abeles, R. H. In Enzyme Activated Irreversible Inhibitors; Seiler, N., Jung, M. J., Koch-Weser, J., Eds.; Elsevier-North-Holland: Amsterdam, 1978; p 1.
    • (1978) Enzyme Activated Irreversible Inhibitors , pp. 1
    • Abeles, R.H.1
  • 37
    • 0001768821 scopus 로고
    • Brodbeck, U., Ed.; Verlag Chim: Weinheim, Germany
    • (d) Ghisla, S.; Wenz, A.; Thorpe, C. In Enzyme Inhibitors; Brodbeck, U., Ed.; Verlag Chim: Weinheim, Germany, 1980; p 43.
    • (1980) Enzyme Inhibitors , pp. 43
    • Ghisla, S.1    Wenz, A.2    Thorpe, C.3
  • 52
    • 2642618521 scopus 로고    scopus 로고
    • note
    • I for the inactivation of MCAD by 19 or 20 based on a similar approach shown in Figure 3 proved to be problematic. The inactivation follows first-order kinetics only at high inhibitor concentration but deviates from the first-order kinetics at low inhibitor concentration. The amount of inhibitor (260 mM) used in the incubations shown in Figure 4 was at the saturation conditions.
  • 66
    • 0030741437 scopus 로고    scopus 로고
    • 20 It should be noted that the apparently greater ring strain associated with the spiropentyl system is misleading since it contains one more cyclopropyl ring than the methylenecyclopropane case. Interestingly, recent calculations showed that the major source of the "strain" resulting from the introduction of a trigonal center into cyclopropane is not the increase in angle strain but the loss of a very strong cyclopropane C-H bond (Johnson, W. T. G.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 5930).
    • (1997) J. Am. Chem. Soc. , vol.119 , pp. 5930
    • Johnson, W.T.G.1    Borden, W.T.2
  • 68
    • 37049100897 scopus 로고
    • Cyclopropylcarbinyl radicals (such as 34) readily undergo β-scission because the SOMO can assume an eclipsed conformation with respect to a β,γ bond. On the contrary, cyclopropyl radicals (such as 35) cannot attain such a conformation without the development of great strain, and therefore, β-scission is hampered due to a much higher activation energy (Kennedy, A. J.; Walton, J. C.; Ingold, K. U. J. Chem. Soc., Perkin Trans. 2 1982, 751).
    • (1982) J. Chem. Soc., Perkin Trans. 2 , pp. 751
    • Kennedy, A.J.1    Walton, J.C.2    Ingold, K.U.3
  • 73
    • 0006918587 scopus 로고
    • Edmondson, D. E., McCormick, D. B., Eds.; Walter de Gruyter: Berlin
    • (e) Zeller, H. D.; Ghisla, S. In Flavins and Flavoproteins; Edmondson, D. E., McCormick, D. B., Eds.; Walter de Gruyter: Berlin, 1987; p 161.
    • (1987) Flavins and Flavoproteins , pp. 161
    • Zeller, H.D.1    Ghisla, S.2
  • 74
    • 0006918587 scopus 로고
    • Edmondson, D. E., McCormick, D. B., Eds.; Walter de Gruyter: Berlin
    • The structures listed in Scheme 7 for the inhibitor-enzyme adducts are by no means a complete set of all possible variations. For example, a fully oxidized C-6-substituted flavin has also been proposed as the structure of a minor component isolated from the incubation of MCPA-CoA (5) with MCAD (Zeller, H. D.; Ghisla, S. In Flavins and Flavoproteins; Edmondson, D. E., McCormick, D. B., Eds.; Walter de Gruyter: Berlin, 1987; p 161).
    • (1987) Flavins and Flavoproteins , pp. 161
    • Zeller, H.D.1    Ghisla, S.2
  • 75
    • 2642639532 scopus 로고    scopus 로고
    • Personal communication
    • Ab initio calculations were carried out to compute the energies of primary cyclopropylcarbinyl and tertiary cyclopropyl radicals using an unrestricted Hartree-Fock level of theory with 6-31G* basis set (UHF/6-3/G*). The results suggested that the energy difference is about 5 kcal/mol, favoring the primary cyclopropylcarbinyl radical. These energy differences reflect the bond dissociation energies (BDEs) of primary alkyl C-H versus the tertiary cyclopropyl C-H bonds (Borden, W. T. Personal communication).
    • Borden, W.T.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.