Lipidic inhibitors of human N-myristoyltransferase

Pasha,Mohammed Khysar; Selvakumar,Ponniah; Ashakumary,Lakshmikuttyamma; Qureshi,Mabood; Guziec,Frank S.; Dimmock,Jonathan R.; Felsted,Ronald L.; Glover,Constance J.; Sharma,Rajendra K.

doi:10.3892/ijmm.13.4.557

April 2004 Volume 13 Issue 4

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April 2004 Volume 13 Issue 4

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Article

Lipidic inhibitors of human N-myristoyltransferase

Authors:
- Mohammed Khysar Pasha
- Ponniah Selvakumar
- Lakshmikuttyamma Ashakumary
- Mabood Qureshi
- Frank S. Guziec
- Jonathan R. Dimmock
- Ronald L. Felsted
- Constance J. Glover
- Rajendra K. Sharma
View Affiliations / Copyright

Affiliations: Department of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, Canada
Pages: 557-563
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Published online on: April 1, 2004

https://doi.org/10.3892/ijmm.13.4.557
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Abstract

This study was undertaken in order to identify compounds which inhibit the activity of human myristoyl-CoA:protein N-myristoyltransferase (hNMT). In particular, the structural features of such molecules which contribute to enzyme inhibition were investigated. Two groups of compounds, namely myristic acid and analogs 1-13 and derivatives of myristoyl-CoA 14-19 were evaluated. All compounds were examined using cAMP-dependent protein kinase derived peptide substrate. The IC50 values were <1 µM, between 1 and 100 µM or >100 µM in eight, four and seven compounds, respectively. Of the six myristoyl-CoA analogs, five had IC50 values in the 0.06-0.59 µM range. These molecules were examined using three additional substrates viz pp60src, MARCKS and M2 gene segment of reovirus type 3 which led to results similar to those obtained with the cAMP-dependent protein kinase substrate. On the other hand, evaluation of myristic acid and four related compounds revealed some differences in hNMT-inhibiting properties among the substrates. From the results obtained, the possible manner whereby potent inhibitors interact with the enzyme was formulated thus enabling the design of further analogs as candidate inhibitors of hNMT.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Lipidic inhibitors of human N-myristoyltransferase

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Abstract

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