PMID- 7108896
OWN - NLM
STAT- MEDLINE
DCOM- 19821021
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 25
IP  - 7
DP  - 1982 Jul
TI  - Species- or isozyme-specific enzyme inhibitors. 6. Synthesis and evaluation of 
      two-substrate condensation products as inhibitors of hexokinases and thymidine 
      kinases.
PG  - 801-5
AB  - Syntheses are described of p1-(adenosine-5')-p3-(glucose-6) triphosphate (Ap3 
      glucose), Ap4 glucose, and p1-(adenosine-5')-P3-(thymidine-5') triphosphate 
      (Ap3T). The compounds were not substrates of any of the enzymes used in the 
      present studies. Ap3 glucose and Ap4 glucose were inhibitors of yeast hexokinase 
      (HK) and the rat isozymes HK I-III; in general, they had less affinity for the 
      enzymes than the substrates ATP and glucose. Inhibition constants (Ki values) of 
      Ap3T with rat mitochondrial thymidine kinase (M-TK) and rat cytoplasmic TK (C-TK) 
      were determined for variable thymidine (TdR) with a constant saturating level of 
      ATP and for variable ATP with constant saturating TdR. Ap3T was a potent and 
      selective inhibitor of M-TK [KM (TdR)/Ki = 1.6, KM (ATP)/Ki = 38 with variable 
      ATP; KM (TdR) Ki = 0.06, KM (ATP)/Ki = 1.4 with variable TdR] relative to C-TK 
      [KM (TdR)/Ki = 0.006, KM (ATP)/Ki = 0.7 with variable ATP; KM (TdR)/Ki = 0.001, 
      KM (ATP)/Ki = 0.12 with variable TdR]. Inhibition of M-TK and C-TK by Ap3T 
      differed qualitatively and quantitatively from inhibition under the same 
      conditions by the metabolic feedback inhibitor TdR 5'-triphosphate.
FAU - Hampton, A
AU  - Hampton A
FAU - Hai, T T
AU  - Hai TT
FAU - Kappler, F
AU  - Kappler F
FAU - Chawla, R R
AU  - Chawla RR
LA  - eng
GR  - CA-06927/CA/NCI NIH HHS/United States
GR  - CA-11196/CA/NCI NIH HHS/United States
GR  - RR-05539/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Isoenzymes)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Chemical Phenomena
MH  - Chemistry
MH  - Glucose/metabolism
MH  - Hexokinase/*antagonists & inhibitors
MH  - In Vitro Techniques
MH  - Isoenzymes/antagonists & inhibitors
MH  - Kinetics
MH  - Mitochondria, Liver/enzymology
MH  - Rats
MH  - Thymidine Kinase/*antagonists & inhibitors
EDAT- 1982/07/01 00:00
MHDA- 1982/07/01 00:01
CRDT- 1982/07/01 00:00
PHST- 1982/07/01 00:00 [pubmed]
PHST- 1982/07/01 00:01 [medline]
PHST- 1982/07/01 00:00 [entrez]
AID - 10.1021/jm00349a007 [doi]
PST - ppublish
SO  - J Med Chem. 1982 Jul;25(7):801-5. doi: 10.1021/jm00349a007.