A comparative SAR study of thrombin receptor derived non peptide mimetics: importance of phenyl/guanidino proximity for activity.

Abstract:

:Thrombin, the most potent physiological platelet agonist interacts with cells through a specific G protein-coupled receptor which has been cloned and sequenced. Synthetic thrombin receptor peptides (TRAPs) comprising the first 5 amino acids (SFLLR and SFLLR-NH2) of the new N-terminus tethered ligand of the thrombin receptor that is generated by thrombin's proteolytic activity were found to cause full platelet aggregation. During the screening of novel thrombin receptor derived non-peptide mimetics in the platelet aggregation assay we found that 1-phenylacetyl-4-(6-guanidohexanoyl)-piperazine (1) and 1-(6-guanidohexanoyl)-4-(phenylacetylamidomethyl)-piperidine (2) exerted in vitro antagonist activities (56% and 40% correspondingly) as it is depicted by the platelet aggregation assay. Using Molecular Modeling, the synthetic compounds were overlayed with SFFLR. All three superimposed low energy structures had Phe and Arg amino acids in spatial close proximity. The superimposition results revealed that 1 resembled more the stereoelectronic environment of SFLLR than 2. This difference may be related to their different antagonist efficacy.

journal_name

Amino Acids

journal_title

Amino acids

authors

Alexopoulos K,Matsoukas J,Tselios T,Roumelioti P,Mavromoustakos T,Holada K

doi

10.1007/BF01318860

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

211-20

issue

3

eissn

0939-4451

issn

1438-2199

journal_volume

15

pub_type

杂志文章
  • Mass spectrometric studies on the interaction of cisplatin and insulin.

    abstract::The interaction of antitumor drug, cisplatin (cis-[PtCl2(NH3)2], CDDP) with insulin from porcine pancreas has been investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and high resolution hybrid ion trap/time-of-flight mass spectrometry (MALIDI-TOF/TOF-MS and ESI-IT/TOF MS). The...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-015-2159-y

    authors: Li J,Yue L,Liu Y,Yin X,Yin Q,Pan Y,Yang L

    更新日期:2016-04-01 00:00:00

  • L-methionine as immune supportive supplement: a clinical evaluation.

    abstract::The objective of the study was to test L-methioinine as a possible immune supportive supplement in HIV infected patients by means of a clinical study. A double-blind, placebo-controlled study was designed. The patients (n = 253) from four different trial centres were randomly divided into two groups, active and placeb...

    journal_title:Amino acids

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s00726-006-0390-2

    authors: Van Brummelen R,du Toit D

    更新日期:2007-07-01 00:00:00

  • Oxidative degradation of N(ε)-fructosylamine-substituted peptides in heated aqueous systems.

    abstract::Glycation, or non-enzymatic glycosylation, is a common protein modification formed by reactions between reducing sugars (i.e. aldoses and ketoses) with protein amino groups. Resulting Amadori and Heyns compounds, respectively, can be oxidatively degraded yielding a structurally heterogeneous group of advanced glycatio...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-015-1940-2

    authors: Greifenhagen U,Frolov A,Hoffmann R

    更新日期:2015-05-01 00:00:00

  • Effect of slow-release β-alanine tablets on absorption kinetics and paresthesia.

    abstract::Oral β-alanine (βA) doses larger than 800 mg commonly result in unpleasant sensory symptoms (paresthesia). However, the association of form (pure vs. slow-release) with side-effects has not been fully described. The aim of this single-blinded, randomized three-arm clinical trial was to compare plasma kinetics and symp...

    journal_title:Amino acids

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s00726-011-1169-7

    authors: Décombaz J,Beaumont M,Vuichoud J,Bouisset F,Stellingwerff T

    更新日期:2012-07-01 00:00:00

  • Microglial self-defence mediated through GLT-1 and glutathione.

    abstract::Glutamate is stored in synaptic vesicles in presynaptic neurons. It is released into the synaptic cleft to provide signalling to postsynaptic neurons. Normally, the astroglial glutamate transporters GLT-1 and GLAST take up glutamate to mediate a high signal-to-noise ratio in the synaptic signalling, and also to preven...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-011-0865-7

    authors: Persson M,Rönnbäck L

    更新日期:2012-01-01 00:00:00

  • Is there a role for eIF5A in translation?

    abstract::The putative translation factor eIF5A is essential for cell viability and is highly conserved from archaebacteria to mammals. This factor is the only cellular protein that undergoes an essential posttranslational modification dependent on the polyamine spermidine, called hypusination. This review focuses on the functi...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-007-0533-0

    authors: Zanelli CF,Valentini SR

    更新日期:2007-08-01 00:00:00

  • Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate.

    abstract::Proline dehydrogenase/oxidase (PRODH/POX) is a mitochondrial protein critical to multiple stress pathways. Because of the roles of PRODH/POX in signaling, and its shared localization to the mitochondrial inner membrane with the electron transport chain (ETC), we investigated whether there was a direct relationship bet...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-015-2134-7

    authors: Hancock CN,Liu W,Alvord WG,Phang JM

    更新日期:2016-03-01 00:00:00

  • Comparative metabolomics charts the impact of genotype-dependent methionine accumulation in Arabidopsis thaliana.

    abstract::Methionine (Met) is an essential amino acid for all organisms. In plants, Met also functions as a precursor of plant hormones, polyamines, and defense metabolites. The regulatory mechanism of Met biosynthesis is highly complex and, despite its great importance, remains unclear. To investigate how accumulation of Met i...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-010-0562-y

    authors: Kusano M,Fukushima A,Redestig H,Kobayashi M,Otsuki H,Onouchi H,Naito S,Hirai MY,Saito K

    更新日期:2010-10-01 00:00:00

  • Effect of natural amino alcohols on the yield of essential amino acids and the amino acid pattern in stressed barley.

    abstract::By application with 2-aminoethanol (2-AE) and choline chloride (CC) in pot experiments the effect of drought stress on barley plants was diminished. In treated plants an increase of the grain yield by 14% (2-AE) and 40% (CC) and a decrease of the stress metabolites glycine betaine and trigonelline was observed. Additi...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/BF00807708

    authors: Bergmann H,Machelett B,Leinhos V

    更新日期:1994-10-01 00:00:00

  • Modulation of glutamate receptors: strategies for the development of novel antidepressants.

    abstract::On a biochemical level, conventional antidepressants have been shown to modulate synaptic levels of biogenic amines (i.e., serotonin, norepinephrine, and dopamine), most often by interfering with reuptake processes or inhibiting metabolism. Strategies directed at modulating glutamatergic transmission may overcome the ...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-001-0121-7

    authors: Skolnick P

    更新日期:2002-01-01 00:00:00

  • Cancer therapy and prevention by green tea: role of ornithine decarboxylase.

    abstract::Green tea which is widely consumed in China, Japan and India, contains polyphenolic compounds, which account for 30% of the dry weight of the leaves. Most of the polyphenols are flavanols, of which (-)-epigallocatechin-3-gallate (EGCG) is most abundant. Epidemiological studies revealed that the incidences of stomach a...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s726-002-8197-9

    authors: Bachrach U,Wang YC

    更新日期:2002-01-01 00:00:00

  • The Schöllkopf chiron and transition metal mediated reactions, a powerful combination for stereoselective construction of cyclic alpha-quaternary-alpha-amino acid derivatives.

    abstract::The focus has been on the development of methodology for stereoselective preparation of spiroannulated intermediates of the Schöllkopf chiron and further transformations to cyclic alpha-amino acids. The spiroannulations are effected by Ru(II)-catalysed ring-closing metathesis reactions, by Ru(II)- and Pd(0)-catalysed ...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-007-0512-5

    authors: Undheim K

    更新日期:2008-04-01 00:00:00

  • Expression of ABC-1 transporter is elevated in human glioma cells under irradiation and temozolomide treatment.

    abstract:OBJECTIVE:Chemo-therapeutic treatment of glioma patients has minor success. Little is known about mechanisms of a pronounced resistance of gliomas towards actual therapies, yet. ABC-1 belongs to the group of transporters known to be involved in the export of hydrophobic substances and vascular regulation. This study in...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-005-0171-3

    authors: Trog D,Moenkemann H,Haertel N,Schüller H,Golubnitschaja O

    更新日期:2005-03-01 00:00:00

  • Use ofα-aminoisobutyric acid and isovaline as marker amino acids for the detection of fungal polypeptide antibiotics. Screening ofHypocrea.

    abstract::Filamentous fungi of the genusHypocrea were grown on malt extract/peptone agar, the mycelia were extracted with dichloromethane/methanol, and the extracts were totally hydrolyzed with 6 N HCl (110°C, 24 h). The amino acids (AA) released from peptides were converted into theirN(O)-pen-tafluoropropionyl 1-propyl esters ...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/BF00806923

    authors: Brückner H,Maisch J,Reinecke C,Kimonyo A

    更新日期:1991-06-01 00:00:00

  • The neuronal differentiation process involves a series of antioxidant proteins.

    abstract::Involvement of individual antioxidant proteins (AOXP) and antioxidants in the differentiation process has been already reported. A systematic search strategy for detecting differentially regulated AOXP in neuronal differentiation, however, has not been published so far. The aim of this study was to provide an analytic...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-005-0214-9

    authors: Oh JE,Karlmark Raja K,Shin JH,Hengstschläger M,Pollak A,Lubec G

    更新日期:2005-11-01 00:00:00

  • Maillard reaction products in tissue proteins: new products and new perspectives.

    abstract::The chemical modification of protein by nonenzymatic browning or Maillard reactions increases with age and in disease. Maillard products are formed by reactions of both carbohydrate- and lipid-derived intermediates with proteins, leading to formation of advanced glycation and lipoxidation end-products (AGE/ALEs). Thes...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-003-0017-9

    authors: Thorpe SR,Baynes JW

    更新日期:2003-12-01 00:00:00

  • Tyrosine-kinases in bacteria: from a matter of controversy to the status of key regulatory enzymes.

    abstract::When considering protein phosphorylation in bacteria, phosphorylation of aspartic acid and histidine residues mediated by the two-component systems is the first to spring to mind. And yet other phosphorylation systems have been described in bacteria in the past 20 years including eukaryotic-like serine/threonine kinas...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-009-0237-8

    authors: Bechet E,Guiral S,Torres S,Mijakovic I,Cozzone AJ,Grangeasse C

    更新日期:2009-09-01 00:00:00

  • Immunization with DISC1 protein in an animal model of ADHD influences behavior and excitatory amino acids in prefrontal cortex and striatum.

    abstract::The Disrupted-in-schizophrenia 1 (DISC1) gene is involved in vulnerability to neuropsychiatric disorders. Naples high-excitability (NHE) rat model neuropsychiatric problems characterized by an unbalanced mesocortical dopamine system. Here, we assessed behavioral and neurochemical effects of immunization against multim...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-014-1897-6

    authors: Ruocco LA,Treno C,Gironi Carnevale UA,Arra C,Boatto G,Pagano C,Tino A,Nieddu M,Michel M,Prikulis I,Carboni E,de Souza Silva MA,Huston JP,Sadile AG,Korth C

    更新日期:2015-03-01 00:00:00

  • Enhanced osteoblast adhesion on transglutaminase 2-crosslinked fibronectin.

    abstract::Fibronectin (FN) is a cell adhesion protein that binds integrins in a process also involving the protein-crosslinking enzyme transglutaminase 2 (TG2) as a co-receptor. The cell-adhesive property of TG2 has been linked to a complex formation with FN and to its ability to crosslink and polymerize FN on the cell surface....

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-008-0125-7

    authors: Forsprecher J,Wang Z,Nelea V,Kaartinen MT

    更新日期:2009-04-01 00:00:00

  • Solution structure of a novel α-conotoxin with a distinctive loop spacing pattern.

    abstract::α-Pharmacological conotoxins are among the most selective ligands of nicotinic acetylcholine receptors with typical cysteine frameworks. They are characterized by the intercysteine loop and classified into various subfamilies, such as α3/5 and α4/7 conotoxins. A novel α-conotoxin, Pu14a (DCPPHPVPGMHKCVCLKTC), with a d...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-011-1093-x

    authors: Zhang B,Huang F,Du W

    更新日期:2012-07-01 00:00:00

  • Expression and function of arginine-producing and consuming-enzymes in the kidney.

    abstract::The kidney plays a key role in arginine metabolism. Arginine production is controlled by argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) which metabolize citrulline and aspartate to arginine and fumarate whereas arginine consumption is dependent on arginine:glycine amidinotransferase (GAT), which ...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-011-0897-z

    authors: Levillain O

    更新日期:2012-04-01 00:00:00

  • Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease.

    abstract::Nonalcoholic fatty liver disease (NAFLD) is a globally widespread disease of increasing clinical significance. The pathological progression of the disease from simple steatosis to nonalcoholic steatohepatitis (NASH) has been well defined, however, the contribution of altered branched chain amino acid metabolomic profi...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-014-1894-9

    authors: Lake AD,Novak P,Shipkova P,Aranibar N,Robertson DG,Reily MD,Lehman-McKeeman LD,Vaillancourt RR,Cherrington NJ

    更新日期:2015-03-01 00:00:00

  • Effect of repetitive lysine-tryptophan motifs on the bactericidal activity of antimicrobial peptides.

    abstract::Previous studies identified lysine- and tryptophan-rich sequences within various cationic antimicrobial peptides. In the present study, we synthesized a series of peptides composed of lysine (K)-tryptophan (W) repeats (KW)( n ) (where n equals 2, 3, 4 or 5) with amida...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-012-1388-6

    authors: Gopal R,Seo CH,Song PI,Park Y

    更新日期:2013-02-01 00:00:00

  • Changes in free amino acids in the brain during embryonic development in layer and broiler chickens.

    abstract::Developmental changes in the levels of the excitatory amino acids L-glutamate (Glu) and L-Aspartate (Asp) and inhibitory amino acids glycine (Gly) and gamma-amino butyric acid (GABA), as well as taurine and its related amino acids L-methionine (Met), L-cysteine (Cys) and L-serine (Ser) in the brain and pectoralis musc...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-008-0068-z

    authors: Sato M,Tomonaga S,Denbow DM,Furuse M

    更新日期:2009-02-01 00:00:00

  • In vivo targeting of HER2-positive tumor using 2-helix affibody molecules.

    abstract::Molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression has drawn significant attention because of the unique role of the HER2 gene in diagnosis, therapy and prognosis of human breast cancer. In our previous research, a novel cyclic 2-helix small protein, MUT-DS, was discovered as an anti-...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-011-1096-7

    authors: Ren G,Webster JM,Liu Z,Zhang R,Miao Z,Liu H,Gambhir SS,Syud FA,Cheng Z

    更新日期:2012-07-01 00:00:00

  • Effects of GABA-transaminase inhibitor Vigabatrin on thermoregulation in rats.

    abstract::Vigabatrin is a GABA derivative (gamma-vinyl GABA) which inhibits irreversibly the enzyme activity of GABA transaminase and thus increased indirectly brain GABA concentrations. We have used body temperature assay to examine the effects of Vigabatrin on thermoregulation in intact rats. In order to understand the mechan...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-010-0754-5

    authors: Nikolov RP,Yakimova KS

    更新日期:2011-05-01 00:00:00

  • The inhibitory effect of various indolyl amino acid derivatives on arginase activity in macrophages.

    abstract::Numerous indolyl amino acids and their derivatives inhibited arginase activity. The inhibition was found to be non-competitive, - at least partly - allosteric, and independent on manganese ions in the active site, and it cannot be explained by the dissociation of arginase homotrimers. Indole alone is weakly inhibitory...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-006-0470-3

    authors: Hrabák A,Bajor T,Mészáros G

    更新日期:2008-02-01 00:00:00

  • SILAC-based proteomic analysis to dissect the "histone modification signature" of human breast cancer cells.

    abstract::In living cells, the N-terminal tails of core histones, the proteinaceous component of nucleosomes, are subjected to a range of covalent post-translational modifications (PTMs), which have specific roles in modulating chromatin structure and function. A growing body of evidence suggests that deregulation of histone mo...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-010-0668-2

    authors: Cuomo A,Moretti S,Minucci S,Bonaldi T

    更新日期:2011-07-01 00:00:00

  • Effects of dietary L-arginine or N-carbamylglutamate supplementation during late gestation of sows on the miR-15b/16, miR-221/222, VEGFA and eNOS expression in umbilical vein.

    abstract::Placental vascular formation and blood flow are crucial for fetal survival, growth and development, and arginine regulates vascular development and function. This study determined the effects of dietary arginine or N-carbamylglutamate (NCG) supplementation during late gestation of sows on the microRNAs, vascular endot...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-011-0948-5

    authors: Liu XD,Wu X,Yin YL,Liu YQ,Geng MM,Yang HS,Blachier F,Wu GY

    更新日期:2012-06-01 00:00:00

  • Mapping surface residues of eIF5A that are important for binding to the ribosome using alanine scanning mutagenesis.

    abstract::The translation elongation factor eIF5A is conserved through evolution and is necessary to rescue the ribosome during translation elongation of polyproline-containing proteins. Although the site of eIF5A binding to the ribosome is known, no systematic analysis has been performed so far to determine the important resid...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-016-2279-z

    authors: Barbosa NM,Boldrin PE,Rossi D,Yamamoto PA,Watanabe TF,Serrão VH,Hershey JW,Fraser CS,Valentini SR,Zanelli CF

    更新日期:2016-10-01 00:00:00