Abstract：
:The pivotal role of the Arg-Gly-Asp (RGD) peptide motif in integrin-mediated cell adhesive interactions with extracellular matrix and plasma proteins stimulated the present design of nonpeptidic mimetics of this sequence. To probe the structural requirements for RGD recognition by integrins, we designed various structural mimetics of the tripeptide sequence, which consist of differentially spaced guanidinium and carboxylic groups. We now report that structures which contain guanidinium and carboxylic groups separated by an 11-carbon atom backbone mimic the distal configuration of functional RGD sequence. These compounds acquire a considerable affinity for the RGD-dependent platelet alpha IIb beta 3 integrin. As a result, these mimetics specifically inhibited platelet aggregation with an IC50 at the submillimolar range and interfered with RGD-dependent adhesion of CD4+ T-lymphocytes and metastatic tumor cells to immobilized fibronectin and vitronectin. A structural mimetic of the Arg-Gly-Glu (RGE) sequence, and structures with incorrect spacing between the functional groups, failed to inhibit these adhesive interactions. Furthermore, substitution of the guanidinium group by a primary amine abrogated the RGD-mediated biological effects. In vivo, an RGD surrogate effectively inhibited the elicitation of a delayed-type hypersensitivity reaction mediated by CD4+ T-cells, while the RGE mimetic did not. This interference suggests for a central role for RGD recognition in the regulation of immune responses. These proteolytically stable RGD mimetics may thus serve as useful therapeutic agents in versatile pathologic processes which depend on RGD recognition.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Greenspoon N,Hershkoviz R,Alon R,Varon D,Shenkman B,Marx G,Federman S,Kapustina G,Lider Odoi
10.1021/bi00055a002subject
Has Abstractpub_date
1993-02-02 00:00:00pages
1001-8issue
4eissn
0006-2960issn
1520-4995journal_volume
32pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:Spectrophotometric titration of pyridoxamine-pyruvate transaminase (EC 2.6.1.30) with pyridoxal at pH 7.15 gives four equivalent binding sites per tetramer. The pH dependence of the equilibrium constant for the association of 5'-deoxypyridoxal with the active site lysine residue was determined spectrophotometrically. ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00643a013
更新日期：1977-11-29 00:00:00
abstract：:It had been previously reported that aromatic amines were not substrates for the bacterial quinoprotein methylamine dehydrogenase. In this study, benzylamine-dependent activity was also not observed in the steady-state assay of this enzyme with the artificial electron acceptor phenazine ethosulfate (PES). Benzylamines...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00128a012
更新日期：1992-04-07 00:00:00
abstract：:Regions of the negative strands of the satellite RNAs of chicory yellow mottle virus (sCYMV1) and arabis mosaic virus (sArMV) have similarity in sequence and predicted secondary structure compared to the tobacco ringspot virus satellite RNA (sTRSV) hairpin ribozyme, suggesting that they may also be catalytic RNAs of a...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00048a024
更新日期：1995-12-05 00:00:00
abstract：:The hydrogen exchange behavior of the N-terminal helical segment in horse heart cytochrome c was studied in both the reduced and the oxidized forms by use of two-dimensional nuclear magnetic resonance methods. The amide protons of the first six residues are not H bonded and exchange rapidly with solvent protons. The m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00353a025
更新日期：1986-03-11 00:00:00
abstract：:S-Glutathionylation is a redox-regulated modification that uncouples endothelial nitric oxide synthase (eNOS), switching its function from nitric oxide (NO) synthesis to (•)O2(-) generation, and serves to regulate vascular function. While in vitro or in vivo eNOS S-glutathionylation with modification of Cys689 and Cys...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi400404s
更新日期：2013-09-24 00:00:00
abstract：:Many naturally occurring RNA structures contain single mismatches. However, the algorithms currently used to predict RNA structure from sequence rely on a minimal set of data for single mismatches, most of which occur rather infrequently in nature. As a result, several approximations and assumptions are used to predic...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi701311c
更新日期：2007-11-20 00:00:00
abstract：:The beta-glucosidase from Agrobacterium sp. catalyzes the hydrolysis of beta-glucosides via a covalent alpha-D-glucopyranosyl-enzyme intermediate involving Glu358. Hydrolysis of 2,4-dinitrophenyl beta-D-glucopyranoside by the low activity Glu358Asp mutant of Agrobacterium beta-glucosidase is accompanied by time-depend...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00044a033
更新日期：1995-11-07 00:00:00
abstract：:The secretion of lung surfactant in alveolar type II cells is a complex process involving the fusion of lamellar bodies with the plasma membrane. This process is somewhat different from the exocytosis of hormones and neurotransmitters. For example, it is a relatively slower process, and lamellar bodies are very large ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi036338y
更新日期：2004-03-30 00:00:00
abstract：:X-ray crystallographic studies have shown that DNA binding by human polymerase beta (pol beta) occurs primarily through two structurally and sequentially homologous helix-hairpin-helix (HhH) motifs, one in the fingers subdomain and the other in the 8-kDa domain [Pelletier, H., Sawaya, M. R., Wolfle, W., Wilson, S. H.,...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi960790i
更新日期：1996-10-01 00:00:00
abstract：:Two intermediates in the biosynthetic pathway to bacterial menaquinones are o-succinylbenzoic acid and 1,4-dihydroxy-2-naphthoic acid. Cell-free extracts have been prepared from Escherichia coli which catalyze the conversion of labeled o-succinylbenzoic acid to the naphthoic acid and also to menaquinones. The naphthoa...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00667a007
更新日期：1976-11-02 00:00:00
abstract：:Z-Ala-Ala-Phe-glyoxal (where Z is benzyloxycarbonyl) has been shown to be a competitive inhibitor of pepsin with a Ki = 89 +/- 24 nM at pH 2.0 and 25 degrees C. Both the ketone carbon (R13COCHO) and the aldehyde carbon (RCO13CHO) of the glyoxal group of Z-Ala-Ala-Phe-glyoxal have been 13C-enriched. Using 13C NMR, it h...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi701000k
更新日期：2007-10-02 00:00:00
abstract：:The serotonin transporter (SERT) is a member of a highly homologous family of proteins responsible for the reuptake of biogenic amines from the synaptic cleft. We took advantage of native restriction sites in SERT to construct a chimeric transporter containing a small (34 amino acid) region of the norepinephrine trans...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi962150l
更新日期：1997-02-11 00:00:00
abstract：:The covalent affinity probe maltosyl isothiocyanate (MITC) has been used previously to identify the glucose transporter of human erythrocytes as a component of band 3. By use of limited proteolysis, the site on the Mr 100 000 protein to which MITC attaches has been localized to a 17 000-dalton region near the center o...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00331a001
更新日期：1985-05-07 00:00:00
abstract：:The compounds 3-hydroxy-4-nitrobenzaldehyde and 3-hydroxy-4-nitrobenzyl alcohol are introduced as new chromophoric substrates for probing the catalytic mechanism of horse liver alcohol dehydrogenase (LADH). Ionization of the phenolic hydroxyl group shifts the spectrum of the aldehyde from 360 to 433 nm (pKa = 6.0), wh...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00385a017
更新日期：1987-06-02 00:00:00
abstract：:Complement components C5b-6 and C7 assemble to form C5b-7, which then interacts with membranes and commits the membrane attack complex to a target site. This protein-membrane association event was investigated to determine possible structural features that could contribute to a selective membrane attack. This system m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00371a065
更新日期：1986-11-18 00:00:00
abstract：:We have measured the pH-dependent (1)H, (13)C, and (15)N NMR spectra of pyridoxal 5'-phosphate ((13)C(2)-PLP) mixed with equal amounts of either doubly (15)N-labeled diaminopropane, (15)N(α)-labeled l-lysine, or (15)N(ε)-labeled l-lysine as model systems for various intermediates of the transimination reaction in PLP-...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi101061m
更新日期：2010-12-28 00:00:00
abstract：:Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iro...
journal_title：Biochemistry
pub_type： 杂志文章,评审
doi：10.1021/bi300752r
更新日期：2012-07-24 00:00:00
abstract：:Trinucleotide repeat expansion diseases (TREDs) are correlated with elongation of CNG DNA and RNA repeats to pathological level. This paper shows, for the first time, complete data concerning thermodynamic stabilities of RNA with CNG trinucleotide repeats. Our studies include the stability of oligoribonucleotides comp...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0502339
更新日期：2005-08-16 00:00:00
abstract：:The active-site zinc in human glutathione-dependent formaldehyde dehydrogenase (FDH) undergoes coenzyme-induced displacement and transient coordination to a highly conserved glutamate residue (Glu-67) during the catalytic cycle. The role of this transient coordination of the active-site zinc to Glu-67 in the FDH catal...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi052554q
更新日期：2006-04-18 00:00:00
abstract：:Factor XII was purified approximately 14 000-fold from bovine plasma by ammonium sulfate fractionation followed by heparin-agarose, DEAE-Sephadex, CM-cellulose, arginine-agarose, and benzamidine-agarose column chromatography. By this method, about 15 mg of protein was purified from 15 L of plasma with an overall yield...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00629a036
更新日期：1977-05-17 00:00:00
abstract：:alpha 1-Adrenergic receptor probes, which can be radioiodinated to yield high specific activity radioligands, have been synthesized and characterized. 2-[4-(4-Amino-benzoyl)piperazin-1-yl]-4-amino-6,7-dimethoxyquin azoline (CP63,155), an arylamine analogue of the selective alpha 1-adrenergic antagonist prazosin, and i...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00311a031
更新日期：1984-07-31 00:00:00
abstract：:A conformational change in the DNA plasmid ColE1 appears to occur upon specific binding of the restriction endonuclease EcoRI. Enzyme association alters the chiral discrimination found in binding metallointercalators to DNA sites. The complexes tris(1,10-phenanthroline)ruthenium(II), Ru(phen)3(2+), tris(4,7-diphenyl-1...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00356a053
更新日期：1986-04-22 00:00:00
abstract：:Previous work has indicated that PEP mutase catalyzes the rearrangement of phosphoenolpyruvate to phosphonopyruvate by a dissociative mechanism. The crystal structure of the mutase with Mg(II) and sulfopyruvate (a phosphonopyruvate analogue) bound showed that the substrate is anchored to the active site by the Mg(II),...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi036255h
更新日期：2004-04-20 00:00:00
abstract：:The conformation of two fragments derived from anti-poly(D-alanyl) antibodies, the divalent fragment (Fab')2 and the monovalent fragment Fab', was studied by small-angle X-ray scattering before and after interaction with the tetra-D-alanine amide hapten. More than 90% of the combining sites were occupied by the hapten...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00677a035
更新日期：1975-03-25 00:00:00
abstract：:Human plasma phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs). We determined phospholipid transfer activity and HDL binding ability in wild-type PLTP and in 16 PLTP variants created by replacing 12 charged amino acids by site-directed mutag...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi027006g
更新日期：2003-04-22 00:00:00
abstract：:One of the key pathological features of Alzheimer's disease is the aggregation of tau protein. We are therefore searching for compounds capable of inhibiting this reaction. On the basis of an initial screen of 200000 compounds [Pickhardt, M., Gazova, Z., von Bergen, M., Khlistunova, I., Wang, Y., Hascher, A., Mandelko...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi700878g
更新日期：2007-09-04 00:00:00
abstract：:It is known that the proapoptotic protein Bax facilitates the formation of pores in bilayers, resulting in the release of proteins from the intermitochondrial space. We demonstrate that another consequence of the interaction of Bax with membranes is an increase in the rate of lipid transbilayer diffusion. We use two i...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035348w
更新日期：2003-12-16 00:00:00
abstract：:Conformational alterations occurring in bovine alpha 2-macroglobulin (alpha 2M) resulting from proteolysis and nucleophilic modification have been monitored by UV difference spectra, circular dichroism, and changes in the fluorescence of 6-(p-toluidino)-2-naphthalenesulfonate (TNS) and bis(8-anilino-1-naphthalenesulfo...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00321a061
更新日期：1984-12-18 00:00:00
abstract：:Linker histones bind to the nucleosomes and linker DNA of chromatin fibers, causing changes in linker DNA structure and stabilization of higher order folded and oligomeric chromatin structures. Linker histones affect chromatin structure acting primarily through their approximately 100-residue C-terminal domain (CTD). ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi801636y
更新日期：2009-01-13 00:00:00
abstract：:Human methionine synthase reductase (MSR), a diflavin oxidoreductase, plays a vital role in methionine and folate metabolism by sustaining methionine synthase (MS) activity. MSR catalyzes the oxidation of NADPH and shuttles electrons via its FAD and FMN cofactors to inactive MS-cob(II)alamin. A conserved aromatic resi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi2012228
更新日期：2011-12-27 00:00:00
