Structure-Activity Analysis of Guanidine Group in Agmatine for Brain Agmatinase

M. J. Huang, S. Regunathan, M. Botta, K. Lee, E. McClendon, G. B. Yi, M. L. Pedersen, David B Berkowitz, G. Wang, M. Travagli, J. E. Piletz

Research output: Contribution to journalArticle

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Abstract

To identify a selective inhibitor of mammalian agmatinase, screening was performed on four analogues of agmatine with modifications directly to the guanidine group, six analogues with modifications to the carbon-amine chain, and one analogue with modifications at both ends of the molecule. Control compounds were aminoguanidine and 7-nitroindazole, known inhibitors of the three isoforms (i, e, n) of nitric oxide synthase (NOS), and arcaine, a known inhibitor of the glutamate NMDA receptor. These compounds were compared for inhibition of rat agmatinase and arginine decarboxylase (ADC) activities. Results were studied by ab initio Hartee-Fock descriptors based on optimized geometries and van der Waals radii. Linear correlations were obtained using various geometric and electronic descriptors of the carbon (C), nitrogen (N), and hydrogen (H) atoms in the guanidine moiety. The best fit equation for percent activity remaining of rat agmatinase was = 0.3225 D + 72.76 D1916 + 64.97 D1920 - 192.58 H21 - 253.09 (r = 0.89), where D is the calculated dipole moment, D1916 and D1920 are the N19-N16 and N19-N20 distances, respectively, and H21 is the charge on H21. This agmatinase equation is distinct from the equations fit for ADC, the three NOS isoforms, and inhibition of NMDA receptor binding.

Original languageEnglish (US)
Pages (from-to)52-63
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume1009
DOIs
StatePublished - Jan 1 2003

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Agmatine
Guanidine
Brain
N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase
Rats
Protein Isoforms
Carbon
Dipole moment
Glutamate Receptors
Amines
Glutamic Acid
Hydrogen
Screening
Nitrogen
Atoms
Molecules
Geometry
agmatinase
Equations

Keywords

  • Agmatinase
  • Agmatine
  • Arginine decarboxylase
  • Guanidine
  • NMDA receptor
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Huang, M. J., Regunathan, S., Botta, M., Lee, K., McClendon, E., Yi, G. B., ... Piletz, J. E. (2003). Structure-Activity Analysis of Guanidine Group in Agmatine for Brain Agmatinase. Annals of the New York Academy of Sciences, 1009, 52-63. https://doi.org/10.1196/annals.1304.006

Structure-Activity Analysis of Guanidine Group in Agmatine for Brain Agmatinase. / Huang, M. J.; Regunathan, S.; Botta, M.; Lee, K.; McClendon, E.; Yi, G. B.; Pedersen, M. L.; Berkowitz, David B; Wang, G.; Travagli, M.; Piletz, J. E.

In: Annals of the New York Academy of Sciences, Vol. 1009, 01.01.2003, p. 52-63.

Research output: Contribution to journalArticle

Huang, MJ, Regunathan, S, Botta, M, Lee, K, McClendon, E, Yi, GB, Pedersen, ML, Berkowitz, DB, Wang, G, Travagli, M & Piletz, JE 2003, 'Structure-Activity Analysis of Guanidine Group in Agmatine for Brain Agmatinase', Annals of the New York Academy of Sciences, vol. 1009, pp. 52-63. https://doi.org/10.1196/annals.1304.006
Huang, M. J. ; Regunathan, S. ; Botta, M. ; Lee, K. ; McClendon, E. ; Yi, G. B. ; Pedersen, M. L. ; Berkowitz, David B ; Wang, G. ; Travagli, M. ; Piletz, J. E. / Structure-Activity Analysis of Guanidine Group in Agmatine for Brain Agmatinase. In: Annals of the New York Academy of Sciences. 2003 ; Vol. 1009. pp. 52-63.
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