Synthesis of dehydrodipeptides as potential suicide substrates for D, D-peptidases

2011 ◽  
Vol 7 (2) ◽  
Author(s):  
MES Koker
Keyword(s):  
Suicide Substrates

Kinetics of suicide substrates

1990 ◽  
Vol 147 (4) ◽  
pp. 497-508 ◽  
Author(s):  
Zhi-Xin Wang
Keyword(s):  
Kinetics Of ◽  
Suicide Substrates

19-acetylenic, 19-hydroxy-androst-4-en-3,17-diones. Potential suicide substrates of estrogen biosynthesis

1979 ◽  
Vol 20 (23) ◽  
pp. 2105-2108 ◽  
Author(s):  
Douglas F. Coveyy ◽  
Vinod D. Parikh ◽  
Walter W. Chien
Keyword(s):  
Estrogen Biosynthesis ◽  
Suicide Substrates

Suicide substrates for the alanine racemase of Escherichia coli B

Biochemistry ◽  
1978 ◽  
Vol 17 (7) ◽  
pp. 1313-1321 ◽  
Author(s):  
Elizabeth Wang ◽  
Christopher Walsh
Keyword(s):  
Escherichia Coli ◽  
Alanine Racemase ◽  
Escherichia Coli B ◽  
Suicide Substrates

scholarly journals Kinetics of suicide substrates. Practical procedures for determining parameters

1985 ◽  
Vol 227 (3) ◽  
pp. 843-849 ◽  
Author(s):  
S G Waley
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Experimental Error ◽  
Simulated Data ◽  
Steady State Kinetics ◽  
Linear Plot ◽  
Series Of Experiments ◽  
Kinetics Of ◽  
Competing Reactions ◽  
Suicide Substrates

Many clinically important or mechanistically interesting inhibitors react with enzymes by a branched pathway in which inactivation of the enzyme and formation of product are competing reactions. The steady-state kinetics for this pathway [Waley (1980) Biochem. J. 185, 771-773] gave equations for progress curves that were cumbersome. A convenient linear plot is now described. The time (t1/2) for 50% inactivation of the enzyme (this is also the time for 50% formation of product), or for 50% loss of substrate, is measured in a series of experiments in which the concentration of inhibitor, [I]0, is varied; in these experiments the ratio of the concentration of enzyme to the concentration of inhibitor is kept fixed. Then a plot of [I]0 X t1/2 against [I]0 is linear, and the kinetic parameters can be found from the slope and intercept. Furthermore, simplifications of the equations for progress curves are described that are valid when the concentration of inhibitors is high, or is low, or when the extent of reaction is low. The use of simulated data has shown that the recommended methods are not unduly sensitive to experimental error.

scholarly journals Steroidal antibiotics are antimetabolites of Acanthamoeba steroidogenesis with phylogenetic implications

2019 ◽  
Vol 60 (5) ◽  
pp. 981-994 ◽  
Author(s):  
Wenxu Zhou ◽  
Emilio Ramos ◽  
Xunlu Zhu ◽  
Paxtyn M. Fisher ◽  
Medhanie E. Kidane ◽  
...  
Keyword(s):  
Animal Studies ◽  
Acanthamoeba Castellanii ◽  
Chemical Kinetic ◽  
Ergosterol Biosynthesis ◽  
Binding Studies ◽  
Product Specificity ◽  
Phylogenetic Implications ◽  
Olefin Production ◽  
Novel Scaffold ◽  
Suicide Substrates

Pathogenic organisms may be sensitive to inhibitors of sterol biosynthesis, which carry antimetabolite properties, through manipulation of the key enzyme, sterol methyltransferase (SMT). Here, we isolated natural suicide substrates of the ergosterol biosynthesis pathway, cholesta-5,7,22,24-tetraenol (CHT) and ergosta-5,7,22,24(28)-tetraenol (ERGT), and demonstrated their interference in Acanthamoeba castellanii steroidogenesis: CHT and ERGT inhibit trophozoite growth (EC50 of 51 nM) without affecting cultured human cell growth. Washout experiments confirmed that the target for vulnerability was SMT. Chemical, kinetic, and protein-binding studies of inhibitors assayed with 24-AcSMT [catalyzing C28-sterol via Δ24(28)-olefin production] and 28-AcSMT [catalyzing C29-sterol via Δ25(27)-olefin production] revealed interrupted partitioning and irreversible complex formation from the conjugated double bond system in the side chain of either analog, particularly with 28-AcSMT. Replacement of active site Tyr62 with Phe or Leu residues involved in cation-π interactions that model product specificity prevented protein inactivation. The alkylating properties and high selective index of 103 for CHT and ERGT against 28-AcSMT are indicative of a new class of steroidal antibiotic that, as an antimetabolite, can limit sterol expansion across phylogeny and provide a novel scaffold in the design of amoebicidal drugs. Animal studies of these suicide substrates can further explore the potential of their antibiotic properties.

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