نتایج جستجو برای: alkylation
تعداد نتایج: 5091 فیلتر نتایج به سال:
A summary of recent investigations of the duocarmycins is provided including the total synthesis of (+)-and ent-(-)-duocarmycin SA, the preparation and evaluation of the minimum potent pharmacophore of the alkylation subunit constituting the common pharmacophore of duocarmycin A and SA, the definition and characterization of the DNA alkylation properties of the agents and their correlation with...
The research reported here demonstrates covalent binding to the metal-binding protein metallothionein (MT) by the therapeutic nitrogen mustard mechlorethamine. The most surprising aspect of this interaction is the selectivity of the alkylating agent for specific residues of MT. A combination of MS and proteolytic and enzymatic methods was used to deduce specific locations of mechlorethamine alk...
determine the molecular basis for the cytotoxic action that produces the antitumor effect. Unfortunately, there is pres ently no direct way to identify with certainty the critical molecular lesions. It is, however, possible to obtain comrel ative evidence between molecular effects and cytotoxic effects in various cell types, which could lead to a probable identification of the critical lesions....
Translesion DNA synthesis (TLS), facilitated by low-fidelity polymerases, is an important DNA damage tolerance mechanism. Here, we investigated the role and biological function of TLS polymerase ImuC (former DnaE2), generally present in bacteria lacking DNA polymerase V, and TLS polymerase DinB in response to DNA alkylation damage in Pseudomonas aeruginosa and P. putida. We found that TLS DNA p...
The substituted cysteine accessibility approach, combined with chemical modification using membrane-impermeant alkylating reagents, was used to identify functionally important structural elements of the rat type IIa Na(+)/P(i) cotransporter protein. Single point mutants with different amino acids replaced by cysteines were made and the constructs expressed in Xenopus oocytes were tested for fun...
The first iridium-catalyzed enantioselective allylic alkylation of an olefinic C(sp2)–H bond – that ?,?-unsaturated carbonyl compound, is developed in cooperation with Lewis base catalysis.
Functionalized chiral diazaphospholanes ligate to a variety of transition metals, yielding chiral, catalytically active, metal complexes. Previous work has established that amino acid derivatization of the carboxyl groups of (R,R)-N,N'-phthaloyl-2,3-(2-carboxyphenyl)-phenyl-3,4-diazaphospholane (1) yields phosphines that are excellent ligands for palladium-catalyzed asymmetric allylic alkylatio...
Polymerase α is an essential enzyme mainly mediating Okazaki fragment synthesis during lagging strand replication. A specific point mutation in Schizosaccharomyces pombe polymerase α named swi7-1, abolishes imprinting required for mating-type switching. Here we investigate whether this mutation confers any genome-wide defects. We show that the swi7-1 mutation renders cells hypersensitive to the...
Primary astrocyte cultures were used to investigate the modulation of DNA repair as a tool for sensitizing astrocytes to genotoxic agents. Base excision repair (BER) is the principal mechanism by which mammalian cells repair alkylation damage to DNA and involves the processing of relatively nontoxic DNA adducts through a series of cytotoxic intermediates during the course of restoring normal DN...
Conditions leading to cleavage of all of the disulfide bridges in ribonuclease and several other proteins (0.32 M Z-mercaptoethanol in 8 M urea) caused in papain only partial reduction of the disulfide bonds. Electrophoretic studies indicated that alkylation of the partially reduced derivative yielded a unique molecular species (3-RCM papain) in which one specific disulfide bond had been split,...
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