Title
Inhibitors of protein: Arnesyl transferase and protein:geranylgeranyl transferase I : Synthesis of homologous diphosphonate analogs of isoprenylated pyrophosphate
Author
Overhand, M.
Stuivenberg, H.R.
Pieterman, E.
Cohen, L.H.
van Leeuwen, R.E.W.
Valentijn, A.R.P.M.
Overkleeft, H.S.
van der Marel, G.A.
van Boom, J.H.
Gaubius Instituut TNO
Publication year
1998
Abstract
Novel diphosphonate homologs 7a-7c, and their cyclic counterparts 8a- 8c, of the previously synthesized farnesyl pyrophosphate analogs 1 and 2 were prepared and tested for their inhibition potency and specificity of the enzymes PFT and PGGT-I. Compound 2 was shown to be the most potent inhibitor of PFT (1C50=0.58 ± 0.45 μM) in this series. The novel compound 7a, the one carbon homolog of 2, proved to be the most potent inhibitor of PGGT-I (IC50 = 0.98 ± 0.01 μM). The cyclic analogs 8a-8c are generally less biologically active. The compounds 2 and 7a are nonspecific toward inhibition of PFT and PGGT-I and may inhibit both farnesylation and geranylgeranylation processing of oncogenic proteins.
Subject
Health
bisphosphonic acid derivative
enzyme inhibitor
geranyltransferase
protein farnesyltransferase
article
enzyme activity
enzyme inhibition
enzyme specificity
phosphate metabolism
priority journal
To reference this document use:
http://resolver.tudelft.nl/uuid:7bfa0a40-72c8-40f3-b366-f24e850418f6
DOI
https://doi.org/10.1006/bioo.1998.1101
TNO identifier
234651
ISSN
0045-2068
Source
Bioorganic Chemistry, 26 (5), 269-282
Document type
article