Structural analogs of 5'-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation

Michael W. White; Arthur A. Vandenbark; Carolyn L. Barney; Adolph J. Ferro

doi:10.1016/0006-2952(82)90151-4

Structural analogs of 5'-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation

Michael W. White, Arthur A. Vandenbark, Carolyn L. Barney, Adolph J. Ferro

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

5'-Deoxy-5'-methylthioadenosine (MTA) phosphorylase was purified 13.4-fold from human peripheral lymphocytes. The enzyme demonstrated normal Michaelis-Menten kinetics with K_m values of 26 μM and 7.5 mM for the two substrates. MTA and phosphate, respectively. The rate of MTA degradation was temperature dependent, 47° being the optimum temperature. Five structural analogs served as alternative substrates with K_m values ranging from 31 to 53 μM while two compounds, 5'-deoxy-5'methylthiotubercidin (MTT) (K_i = 31 μM) and adenine (K_i = 172 μM), were inhibitory. These same analogs were examined as inhibitors of mitogen-induced human lymphocyte blastogenesis. MTT was found to be the most effective inhibitor of lymphocyte transformation with an I₅₀ of 80 μM.

Original language	English (US)
Pages (from-to)	503-507
Number of pages	5
Journal	Biochemical Pharmacology
Volume	31
Issue number	4
DOIs	https://doi.org/10.1016/0006-2952(82)90151-4
State	Published - Feb 15 1982
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Pharmacology

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Structural analogs of 5'-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation. / White, Michael W.; Vandenbark, Arthur A.; Barney, Carolyn L.; Ferro, Adolph J.

In: Biochemical Pharmacology, Vol. 31, No. 4, 15.02.1982, p. 503-507.

Research output: Contribution to journal › Article › peer-review

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title = "Structural analogs of 5'-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation",

abstract = "5'-Deoxy-5'-methylthioadenosine (MTA) phosphorylase was purified 13.4-fold from human peripheral lymphocytes. The enzyme demonstrated normal Michaelis-Menten kinetics with Km values of 26 μM and 7.5 mM for the two substrates. MTA and phosphate, respectively. The rate of MTA degradation was temperature dependent, 47° being the optimum temperature. Five structural analogs served as alternative substrates with Km values ranging from 31 to 53 μM while two compounds, 5'-deoxy-5'methylthiotubercidin (MTT) (Ki = 31 μM) and adenine (Ki = 172 μM), were inhibitory. These same analogs were examined as inhibitors of mitogen-induced human lymphocyte blastogenesis. MTT was found to be the most effective inhibitor of lymphocyte transformation with an I50 of 80 μM.",

author = "White, {Michael W.} and Vandenbark, {Arthur A.} and Barney, {Carolyn L.} and Ferro, {Adolph J.}",

note = "Funding Information: Acknowledgemenfs-This research was supported by Grants CA25756a nd CA24151f rom the NationalC ancer Institute.D HEW. and by a ResearchC areerD evelopment Award (~A~417) to A. J. F. from the National Cancer Institute.",

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doi = "10.1016/0006-2952(82)90151-4",

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T1 - Structural analogs of 5'-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation

AU - White, Michael W.

AU - Vandenbark, Arthur A.

AU - Barney, Carolyn L.

AU - Ferro, Adolph J.

N1 - Funding Information: Acknowledgemenfs-This research was supported by Grants CA25756a nd CA24151f rom the NationalC ancer Institute.D HEW. and by a ResearchC areerD evelopment Award (~A~417) to A. J. F. from the National Cancer Institute.

PY - 1982/2/15

Y1 - 1982/2/15

N2 - 5'-Deoxy-5'-methylthioadenosine (MTA) phosphorylase was purified 13.4-fold from human peripheral lymphocytes. The enzyme demonstrated normal Michaelis-Menten kinetics with Km values of 26 μM and 7.5 mM for the two substrates. MTA and phosphate, respectively. The rate of MTA degradation was temperature dependent, 47° being the optimum temperature. Five structural analogs served as alternative substrates with Km values ranging from 31 to 53 μM while two compounds, 5'-deoxy-5'methylthiotubercidin (MTT) (Ki = 31 μM) and adenine (Ki = 172 μM), were inhibitory. These same analogs were examined as inhibitors of mitogen-induced human lymphocyte blastogenesis. MTT was found to be the most effective inhibitor of lymphocyte transformation with an I50 of 80 μM.

AB - 5'-Deoxy-5'-methylthioadenosine (MTA) phosphorylase was purified 13.4-fold from human peripheral lymphocytes. The enzyme demonstrated normal Michaelis-Menten kinetics with Km values of 26 μM and 7.5 mM for the two substrates. MTA and phosphate, respectively. The rate of MTA degradation was temperature dependent, 47° being the optimum temperature. Five structural analogs served as alternative substrates with Km values ranging from 31 to 53 μM while two compounds, 5'-deoxy-5'methylthiotubercidin (MTT) (Ki = 31 μM) and adenine (Ki = 172 μM), were inhibitory. These same analogs were examined as inhibitors of mitogen-induced human lymphocyte blastogenesis. MTT was found to be the most effective inhibitor of lymphocyte transformation with an I50 of 80 μM.

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Structural analogs of 5'-methylthioadenosine as substrates and inhibitors of 5'-methylthioadenosine phosphorylase and as inhibitors of human lymphocyte transformation

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