Abstract:
:New homo- and heterobifunctional cross-linking reagents have been synthesized. These reagents are based on ortho ester, acetal, and ketal functionalities that undergo acid-catalyzed dissociation but are base stable. The protein-reactive group in all the homobifunctional reagents is a maleimide group; the heterobifunctional acetal cross-linker has a maleimide group at one end and an N-hydroxysuccinimide ester at the other. These reagents have been used to cross-link diphtheria toxin (DT) to itself to give covalently cross-linked DT dimer or to conjugate DT monomer to the anti-CD5 antibody, T101. The hydrolysis of these cross-linked proteins was studied as a function of pH. Cleavage rates vary from minutes to hours at the pH of acidified cellular vesicles (approximately pH 5.4), ortho esters being the fastest, acetals the slowest, and ketals intermediate, but the cross-linked products are approximately 100 times more stable at the vascular pH of 7.4 and 1000 times more stable at a storage pH of 8.4 in all cases. The utility of these reagents in the reversible blockade of a toxic protein functional domain was demonstrated by using cross-linked DT dimer where the blocking and unblocking of toxin binding sites correlates with cellular toxicity. Of the different cross-linkers described, the acetone ketal, bis(maleimidoethoxy)propane (BMEP), appears to be the most promising in the construction of highly efficacious immunotoxins.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Srinivasachar K,Neville DM Jrdoi
10.1021/bi00432a023subject
Has Abstractpub_date
1989-03-21 00:00:00pages
2501-9issue
6eissn
0006-2960issn
1520-4995journal_volume
28pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The natural product hypericin is a photosensitive polycyclic aromatic dione compound, which has been widely investigated because of its virucidal and antitumor properties. Although it has been suggested that singlet oxygen or a radical species might be responsible for its biological action, its mechanism of action rem...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991147+
更新日期:1999-08-31 00:00:00
abstract::Benzo[c]phenanthrene diol epoxide can covalently bind to the exocyclic amino group of deoxyadenosine to generate [BPh]dA adducts where the polycyclic aromatic hydrocarbon is attached to the major groove edge of DNA. This paper reports on NMR-energy minimization structural studies of the (+)-trans-anti-[BPh]dA adduct p...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00097a029
更新日期:1993-11-23 00:00:00
abstract::Human alkyladenine DNA glycosylase (AAG) locates and excises a wide variety of structurally diverse alkylated and oxidized purine lesions from DNA to initiate the base excision repair pathway. Recognition of a base lesion requires flipping of the damaged nucleotide into a relatively open active site pocket between two...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101856a
更新日期:2011-03-22 00:00:00
abstract::Structurally diverse small molecules, including 5-(2-benzofuryl)-4-phenyl-1,2,4-triazole-3-thiol (BETT), have been identified via high-throughput screening as activators of caspase-3 in HeLa cell extracts. However, little is known about their mechanism of action. In this study, we investigate how BETT regulates prothy...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9022329
更新日期:2010-03-09 00:00:00
abstract::Guanylin, an intestinal peptide hormone and endogenous ligand of guanylyl cyclase C, is produced as the corresponding prohormone proguanylin. The mature hormone consists of 15 amino acid residues, representing the COOH-terminal part of the prohormone comprised of 94 amino acid residues. Here we report the recombinant ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026434j
更新日期:2002-12-10 00:00:00
abstract::There is considerable evidence that long-range interactions stabilize residual protein structure under denaturing conditions. However, evaluation of the effect of a specific contact on structure in the denatured state has been difficult. Iso-1-cytochrome c variants with a Lys54 → His mutation form a particularly stabl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b01002
更新日期:2017-12-26 00:00:00
abstract::The DNA sequence of the human beta-globin region, comprising over 67 kilobase pairs, has been analyzed for the occurrence of strings of contiguous purine or pyrimidine residues. Tracts of 10 or more contiguous residues are found 4 times more frequently than would be expected with a random distribution of bases, so tha...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00398a050
更新日期:1987-12-01 00:00:00
abstract::All CG dinucleotides along exons 5-8 of the p53 tumor suppressor gene contain endogenous 5-methylcytosine (MeC). These same sites (e.g., codons 157, 158, 245, 248, and 273) are mutational hot spots in smoking-induced lung cancer. Several groups used the UvrABC endonuclease incision assay to demonstrate that methylated...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035259j
更新日期:2004-01-20 00:00:00
abstract::Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first ste...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b01282
更新日期:2016-04-05 00:00:00
abstract::The acid-induced arginine decarboxylase is part of an enzymatic system in Escherichia coli that contributes to making this organism acid resistant. The arginine decarboxylase is a vitamin B(6)-dependent enzyme that is active at acidic pH. It consumes a proton in the decarboxylation of arginine to agmatine, and by work...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900075d
更新日期:2009-05-12 00:00:00
abstract::Recently, we described the formation of a complex between liposomes and the unfolded protein rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1), which could be liberated and efficiently reactivated after treatment of the complex with detergents [Zardeneta, G., & Horowitz, P. M. (1992) Eur. J. Biochem. 210, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00213a025
更新日期:1993-12-21 00:00:00
abstract::Tularemia is a severe infectious disease in humans caused by the Gram-negative bacterium Francisella tularensis (Ft). Because of its low infectious dose, high mortality rate, and the threat of its large-scale dissemination in weaponized form, development of vaccines and immunotherapeutics against Ft is essential. Ft l...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201450v
更新日期:2011-12-20 00:00:00
abstract::Hydroxyl radical induced formation of a DNA-protein cross-link involving thymine and tyrosine in nucleohistone is described. Hydroxyl radicals were generated in N2O-saturated aqueous solution by ionizing radiation. Samples of nucleohistone were hydrolyzed with HCl and trimethylsilylated. Analysis of irradiated samples...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00434a071
更新日期:1989-04-18 00:00:00
abstract::Tryptic digestion studies of the human erythrocyte glucose carrier have shown that a reactive and transport-sensitive exofacial sulfhydryl is located in the carboxy-terminal half of the molecule, corresponding to Cys347, Cys421, or Cys429. In the present studies, the erythrocyte glucose carrier labeled on the exofacia...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00497a014
更新日期:1990-11-13 00:00:00
abstract::(E)-4-Hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH or LytB) catalyzes the terminal step of the MEP/DOXP pathway where it converts (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) into the two products, isopentenyl diphosphate and dimethylallyl diphosphate. The reaction involves the reductive elimination ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi3001215
更新日期:2012-06-19 00:00:00
abstract::Type II dihydrofolate reductases (DHFRs) encoded by the R67 and R388 plasmids are different both in sequence and in structure from known chromosomal DHFRs. These plasmid-derived DHFRs are responsible for conferring trimethoprim resistance to the host strain. A derivative of R388 DHFR, RBG200, has been cloned and overp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00494a011
更新日期:1990-10-23 00:00:00
abstract::Alanine scanning mutagenesis, double mutant cycles, and X-ray crystallography were used to characterize the interface between the anti-hen egg white lysozyme (HEL) antibody D1.3 and HEL. Twelve out of the 13 nonglycine contact residues on HEL, as determined by the high-resolution crystal structure of the D1.3-HEL comp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980148j
更新日期:1998-06-02 00:00:00
abstract::The mechanisms for substrate recognition by two cytoplasmic protein tyrosine phosphatases, PTP-5 and rrbPTP-1, were investigated. Phosphorylation sites on tyrosine-phosphorylated casein, a model PTP substrate, were characterized. Two peptides based on casein phosphorylation sites and one peptide based on the tyrosine ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00097a019
更新日期:1993-11-23 00:00:00
abstract::The proteasome inhibitors, lactacystin and N-acetyl-leucyl-leucyl-norlucinal, caused a rapid and near-complete loss of approximately 22-23-kDa ubiquitinated nucleoproteins, which we have identified as monoubiquitinated nucleosomal histones H2A and H2B by immunological and two-dimensional electrophoretic techniques. In...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970998j
更新日期:1997-11-25 00:00:00
abstract::Sedimentation experiments with closed circular duplex PM2 deoxyribonucleic acid (DNA) and viscosity measurements with sonicated rodlike DNA fragments have been performed to investigate unwinding and extension of the DNA helix associated with binding of homologous series of diacridines. When the acridine nuclei are lin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00566a026
更新日期:1980-12-09 00:00:00
abstract::The X-ray structures of neuronal nitric oxide synthase (nNOS) with N(omega)-hydroxy-l-arginine (l-NHA) and CO (or NO) bound have been determined at 1.91-2.2 A resolution. Microspectrophotometric techniques confirmed reduced redox state and the status of diatomic ligand complexes during X-ray diffraction data collectio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9009743
更新日期:2009-11-03 00:00:00
abstract::Intrinsically disordered proteins (IDPs) are functionally active despite lacking a well-defined three-dimensional structure. Such proteins often undergo a disorder-to-order transition, or induced folding, when binding to their specific physiological partner. Because of cooperativity, the folding and binding steps typi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b00350
更新日期:2017-07-25 00:00:00
abstract::The Ogg1 protein of Saccharomyces cerevisiae belongs to a family of DNA glycosylases and apurinic/apyrimidinic site (AP) lyases, the signature of which is the alpha-helix-hairpin-alpha-helix-Gly/Pro-Asp (HhH-GPD) active site motif together with a conserved catalytic lysine residue, to which we refer as the HhH-GPD/K f...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi992262n
更新日期:2000-02-22 00:00:00
abstract::Miscoding properties induced by estrogen quinone-derived DNA adducts were analyzed using an in vitro experimental system to quantify base substitutions and deletions. Site-specifically modified oligodeoxynucleotides containing a single N2-(2-hydroxyestron-6-yl)-2'-deoxyguanosine (2-OHE1-N2-dG) or N6-(2-hydroxyestron-6...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981235e
更新日期:1998-09-29 00:00:00
abstract::Deletion of Glu146, Thr147, and Trp148 from thrombin dramatically alters its interactions with substrates, ligands, and inhibitors, and the changes appear to result from nonlocal modification of thrombin's structure [Le Bonniec, B. F., Guinto, E. R., & Esmon, C. T. (1992) J. Biol. Chem. 267, 19341-19348]. In an attemp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00179a023
更新日期:1994-04-05 00:00:00
abstract::The C2 domain is a Ca2+-dependent, membrane-targeting motif originally discovered in protein kinase C and recently identified in numerous eukaryotic signal-transducing proteins, including cytosolic phospholipase A2 (cPLA2) of the vertebrate inflammation pathway. Intracellular Ca2+ signals recruit the C2 domain of cPLA...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9717340
更新日期:1997-10-07 00:00:00
abstract::The light chain of activated factor IX (FIXa) is involved in a number of functional properties, including FIXa enzymatic activity. This suggests the existence of a functional link between the FIXa light chain and the catalytic domain. The FIXa structure includes a few putative interactions between EGF2 and the proteas...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060451h
更新日期:2006-09-05 00:00:00
abstract::Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we present structures of the pathogenic SOD1 variants D124V and H80R, both of which demonstrate compromised zinc-binding sites. The disruption of the zinc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100314n
更新日期:2010-07-13 00:00:00
abstract::Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucleotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi901357r
更新日期:2010-01-12 00:00:00
abstract::The ATPase activity of the (Ca2+-Mg2+)-ATPase reconstituted into bilayers of phosphatidylcholines depends on the fatty acyl chain length of the phospholipids. It is shown that the fluorescence response to Ca2+ of the ATPase modified with fluorescein isothiocyanate is also dependent on phospholipid structure and is int...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00371a043
更新日期:1986-11-18 00:00:00