141538-75-2Relevant articles and documents
Novel farnesol and geranylgeraniol analogues: A potential new class of anticancer agents directed against protein prenylation
Gibbs, Barbara S.,Zahn, Todd J.,Mu, YongQi,Sebolt-Leopold, Judith S.,Gibbs, Richard A.
, p. 3800 - 3808 (1999)
Protein farnesyltransferase (FTase), the enzyme responsible for protein farnesylation, has become a key target for the rational design of cancer cheraotherapeutic agents. Herein it is shown that certain novel prenyl diphosphate analogues are potent inhibitors of mammalian FTase. Furthermore, the alcohol precursors of two of these compounds are able to bloch anchorage- independent growth of ras-transformed cells. While 3-allylfarnesol inhibits protein farnesylation, 3-vinylfarnesol instead leads to abnormal prenylation of proteins with the 3-vinylfarnesyl group. In a similar manner, 3- allylgeranylgeraniol acts as a highly specific inhibitor of protein geranylgeranylation, while 3-vinylgeranylgeraniol restores protein geranylgeranylation in cells. This study indicates that certain prenyl alcohol analogues can act as prenyltransferase inhibitors in situ, via a novel prodrug mechanism. These analogues may prove to be valuable tools for investigating the therapeutic consequences of inhibiting geranylgeranylation relative to farnesylation. Furthermore, the 3-vinyl alcohol analogues can inhibit transformed cell growth through a mechanism not involving prenyltransferase inhibition.
Identification of CDP-archaeol synthase, a missing link of ether lipid biosynthesis in Archaea
Jain, Samta,Caforio, Antonella,Fodran, Peter,Lolkema, Juke S.,Minnaard, Adriaan J.,Driessen, Arnold J.M.
supporting information, p. 1392 - 1401 (2014/12/11)
Archaeal membrane lipid composition is distinct from Bacteria and Eukarya, consisting of isoprenoid chains etherified to the glycerol carbons. Biosynthesis of these lipids is poorly understood. Here we identify and characterize the archaeal membrane prote
Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan
Lupoli, Tania J.,Tsukamoto, Hirokazu,Doud, Emma H.,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
supporting information; experimental part, p. 10748 - 10751 (2011/09/13)
The β-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse d-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical d-amino acids can be introduced into the bacterial cell wall.
Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase: Synthesis and biological evaluation of new farnesylpyrophosphate analogues
Duez, Stéphanie,Coudray, La?titia,Mouray, Elisabeth,Grellier, Philippe,Dubois, Jo?lle
experimental part, p. 543 - 556 (2010/05/02)
Protein farnesyltransferase (FTase) has recently appeared as a new target of parasitic diseases, a field poor in drugs in development. With the aim of creating new bisubstrate inhibitors of FTase, new farnesyl pyrophosphate analogues have been studied. Fa
