当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and physical characterization of a P1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases.

Synthesis and physical characterization of a P1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases.

Abstract：

:Serine peptidases are a large, well-studied, and medically important class of peptidases. Despite the attention these enzymes have received, details concerning the substrate specificity of even some of the best known enzymes in this class are lacking. One approach to rapidly characterizing substrate specificity for peptidases is the use of positional scanning combinatorial substrate libraries. We recently synthesized such a library for enzymes with a preference for arginine at P1 and demonstrated the use of this library with thrombin (Edwards et al. Bioorg. Med. Chem. Lett. 2000, 10, 2291). In the present work, we extend these studies by demonstrating good agreement between the theroretical and measured content of portions of this library and by showing that the library permits rapid characterization of the substrate specificity of additional SA clan serine peptidases including factor Xa, tryptase, and trypsin. These results were consistent both with cleavage sites in natural substrates and cleavage of commercially available synthetic substrates. We also demonstrate that pH or salt concentration have a quantitative effect on the rate of cleavage of the pooled library substrates but that correct prediction of optimal substrates for the enzymes studied appeared to be independent of these parameters. These studies provide new substrate specificity data on an important class of peptidases and are the first to provide physical characterization of a peptidase substrate library.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Furlong ST,Mauger RC,Strimpler AM,Liu YP,Morris FX,Edwards PD

doi

10.1016/s0968-0896(02)00174-8

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

3637-47

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968089602001748

journal_volume

10

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Responsive Mn(II) complexes for potential applications in diagnostic Magnetic Resonance Imaging.

    abstract：:The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L(1), L(2) and L(3)) were designed...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.07.064

    authors： Rolla GA,Tei L,Fekete M,Arena F,Gianolio E,Botta M

    更新日期：2011-02-01 00:00:00

  • The chemoenzymatic synthesis of neoglycolipids and lipid-linked oligosaccharides using glycosyltransferases.

    abstract：:The application of glycosyltransferases to the chemoenzymatic synthesis of neoglycosphingolipids and lipid-linked oligosaccharides allows the regio- and stereoselective formation of glycosidic bonds. In our laboratory galactosyl-, sialyl-, and fucosyltransferases have been used to assemble oligosaccharide headgroups d...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)82075-1

    authors： Flitsch SL,Goodridge DM,Guilbert B,Revers L,Webberley MC,Wilson IB

    更新日期：1994-11-01 00:00:00

  • d(G3T4G4) forms unusual dimeric G-quadruplex structure with the same general fold in the presence of K+, Na+ or NH4+ ions.

    abstract：:We have recently communicated that DNA oligonucleotide d(G(3)T(4)G(4)) forms a dimeric G-quadruplex in the presence of K(+) ions [J. Am. Chem. Soc.2003, 125, 7866-7871]. The high-resolution NMR structure of d(G(3)T(4)G(4))(2) G-quadruplex exhibits G-quadruplex core consisting of three stacked G-quartets. The two overh...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.08.009

    authors： Sket P,Crnugelj M,Plavec J

    更新日期：2004-11-15 00:00:00

  • N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A): A PET tracer for imaging brain acetylcholinesterase in vivo.

    abstract：:N-[(18)F]Fluoroethyl-4-piperidyl acetate ([(18)F]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [(18)F]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[(18)F]fluoroethyl bromide ([(18)F]FEtBr) at 130 degrees C for 30 min in 37% r...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00177-9

    authors： Zhang MR,Furutsuka K,Maeda J,Kikuchi T,Kida T,Okauchi T,Irie T,Suzuki K

    更新日期：2003-06-12 00:00:00

  • Synthesis, cellular internalization and photodynamic activity of glucoconjugated derivatives of tri and tetra(meta-hydroxyphenyl)chlorins.

    abstract：:Glucoconjugated tri and tetra(meta-hydroxyphenyl)chlorins have been synthesized in order to explore how glucoconjugation of the macrocycle affects the photoactivity of the molecule. Internalization processes, photosensitizing efficacy of TPC(m-O-GluOH)(3) and TPC(m-O-GluOH)(4), in HT29 human adenocarcinoma cells have ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00050-6

    authors： Laville I,Figueiredo T,Loock B,Pigaglio S,Maillard P,Grierson DS,Carrez D,Croisy A,Blais J

    更新日期：2003-04-17 00:00:00

  • Synthesis of plaunotol derivatives and their antibacterial activities against Helicobacter pylori.

    abstract：:Plaunotol, a known antiulcer drug, has antibacterial activities against Helicobacter pylori. Plaunotol thiourea derivatives 2--4 and diol derivatives 6--10 were designed in search for a compound with high antibacterial activities. Thiourea derivatives 2--4 were synthesized regioselectively using our effective syntheti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00080-3

    authors： Tago K,Minami E,Masuda K,Akiyama T,Kogen H

    更新日期：2001-07-01 00:00:00

  • Construction of a chemically and conformationally self-replicating system of amyloid-like fibrils.

    abstract：:The amyloid-like fibril is considered to be a macromolecular self-assemblage with a highly-ordered quaternary structure, in which numerous beta-stranded polypeptide chains align regularly. Therefore, this kind of fibril has the potential to be engineered into proteinaceous materials, although conformational alteration...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.11.022

    authors： Takahashi Y,Mihara H

    更新日期：2004-02-15 00:00:00

  • Isolation and characterization of a monoamine oxidase B selective inhibitor from tobacco smoke.

    abstract：:It is well established that tobacco smokers have reduced levels of monoamine oxidase activities both in the brain and peripheral organs. Furthermore, extensive evidence suggests that smokers are less prone to develop Parkinson's disease. These facts, plus the observation that inhibition of monoamine oxidase B protects...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.12.057

    authors： Khalil AA,Davies B,Castagnoli N Jr

    更新日期：2006-05-15 00:00:00

  • 1-[2-Hydroxy-3-octadecan-1'-oate]propyl-2'',2'',5'',5''-tetramethyl pyrolidine-N-oxyl-3''-carboxylate as a potential spin probe for membrane structure studies.

    abstract：:The synthesis of a new minimum steric perturbing proxyl nitroxide, which is a derivative of glycerol and contains a stearic acid moiety, has been carried out. Its localization in model membrane L-alpha-dipalmitoyl phosphatidyl choline (DPPC) was ascertained with the help of ESR, DSC, 1H and 31P NMR techniques. The nit...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00216-3

    authors： Katoch R,Trivedi GK,Phadke RS

    更新日期：1999-12-01 00:00:00

  • Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds.

    abstract：:V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.06.031

    authors： Niculescu-Duvaz D,Niculescu-Duvaz I,Suijkerbuijk BM,Ménard D,Zambon A,Nourry A,Davies L,Manne HA,Friedlos F,Ogilvie L,Hedley D,Takle AK,Wilson DM,Pons JF,Coulter T,Kirk R,Cantarino N,Whittaker S,Marais R,Springer CJ

    更新日期：2010-09-15 00:00:00

  • Synthesis, stability and in vitro dermal evaluation of aminocarbonyloxymethyl esters as prodrugs of carboxylic acid agents.

    abstract：:Aminocarbonyloxymethyl esters based on (S)-amino acid carriers were synthesised and evaluated as potential prodrugs of carboxylic acid agents. In addition, the compounds were evaluated as topical prodrugs with the aim of improving the dermal delivery of two non-steroidal anti-inflammatory agents: naproxen and flufenam...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00336-4

    authors： Mendes E,Furtado T,Neres J,Iley J,Jarvinen T,Rautio J,Moreira R

    更新日期：2002-03-01 00:00:00

  • Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis.

    abstract：:The Wnt signaling pathway plays a key role in organ and tissue homeostasis, and when dysregulated, can become a major underlying mechanism of disease, particularly cancer. We reported previously that the anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.01.046

    authors： Mook RA Jr,Ren XR,Wang J,Piao H,Barak LS,Kim Lyerly H,Chen W

    更新日期：2017-03-15 00:00:00

  • Systematic synthesis of N-methyl-1-deoxynojirimycin-containing, Le(x), Le(a), sialyl-Le(x) and sialyl-Le(a) epitopes recognized by selectins.

    abstract：:A systematic synthesis of the N-methyl-1-deoxynojirimycin-containing oligosaccharides related to the Lewis x, Lewis a, sialyl-Lewis x and sialyl-Lewis a antigens has been achieved. The couplings of the suitably protected 1-deoxynojirimycin derivative 10 with methyl-1-thioglycosides (glycosyl donors) of L-fucose (11), ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)82080-5

    authors： Kiso M,Furui H,Ando K,Ishida H,Hasegawa A

    更新日期：1994-11-01 00:00:00

  • Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes.

    abstract：:The effects of Brazilian green propolis ethanol extract on Cry j1-induced cys-leukotrienes and histamine release from peripheral leukocytes of patients with allergic rhinitis were investigated. One of the key mechanisms for the anti-allergic properties of the extract was revealed to be the suppression of cys-LTs relea...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.11.007

    authors： Tani H,Hasumi K,Tatefuji T,Hashimoto K,Koshino H,Takahashi S

    更新日期：2010-01-01 00:00:00

  • Discovery of an 8-methoxytetrahydroisoquinoline derivative as an orally active N-type calcium channel blocker for neuropathic pain without CYP inhibition liability.

    abstract：:In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-{[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone ((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.05.053

    authors： Ogiyama T,Yonezawa K,Inoue M,Katayama N,Watanabe T,Yoshimura S,Gotoh T,Kiso T,Koakutsu A,Kakimoto S,Shishikura JI

    更新日期：2015-08-01 00:00:00

  • 8-Substituted 2-alkynyl-N(9)-propargyladenines as A2A adenosine receptor antagonists.

    abstract：:Structure-activity relationships of 2-alkynyladenine derivatives were explored by varying substituents at the 9-, 8- and 2-positions of the purine moiety in order to optimize A2A adenosine receptor antagonist activity in vitro. A propargyl group at the 9-position was found to be important for A2A antagonist activity, ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.04.041

    authors： Endo K,Deguchi K,Matsunaga H,Tomaya K,Yamada K

    更新日期：2014-06-15 00:00:00

  • Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel.

    abstract：:Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive an...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.07.069

    authors： Sun L,Veith JM,Pera P,Bernacki RJ,Ojima I

    更新日期：2010-10-01 00:00:00

  • Synthesis and antiviral evaluation of 2-amino-6-carbamoylpurine dioxolane nucleoside derivatives and their phosphoramidates prodrugs.

    abstract：:The synthesis of 9-(β-d-1,3-dioxolan-4-yl)2,6-diaminopurine nucleoside phosphoramidate prodrugs as well as various 2-amino-6-carbamoylpurine dioxolane derivatives and their phosphoramidates prodrugs is reported. Their ability to block HIV and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.10.003

    authors： Cho JH,Bondana L,Detorio MA,Montero C,Bassit LC,Amblard F,Coats SJ,Schinazi RF

    更新日期：2014-12-01 00:00:00

  • Design and synthesis of marine fungal phthalide derivatives as PPAR-γ agonists.

    abstract：:On the basis of a marine fungal phthalide (paecilocin A) skeleton, we synthesized 20 analogs and evaluated them for peroxisome proliferator-activated receptor gamma (PPAR-γ) binding and activation. Among these analogs, 6 and 7 had significant PPAR-γ binding activity, and 7 showed further PPAR-γ activation in rat liver...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.06.039

    authors： Xiao B,Yin J,Park M,Liu J,Li JL,Kim EL,Hong J,Chung HY,Jung JH

    更新日期：2012-08-15 00:00:00

  • Application of enzymatically stable dipeptides for enhancement of intestinal permeability. Synthesis and in vitro evaluation of dipeptide-coupled compounds.

    abstract：:Transport across the intestinal barrier of compounds with low permeability may be facilitated by targeting the human oligopeptide transporter, hPepT1. A flexible synthetic pathway for attaching compounds to dipeptides through ester or amide bonds was developed. Furthermore, a synthetic approach to functionalize model ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00066-9

    authors： Friedrichsen GM,Jakobsen P,Taub M,Begtrup M

    更新日期：2001-10-01 00:00:00

  • Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway.

    abstract：:We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable properties. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory acti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.001

    authors： Mahindroo N,Connelly MC,Punchihewa C,Yang L,Yan B,Fujii N

    更新日期：2010-07-01 00:00:00

  • Tyrosinase inhibitory activity of a 6-isoprenoid-substituted flavanone isolated from Dalea elegans.

    abstract：:To aid the pharmaceutical and cosmetic industry in the development of alternatives to prevent melanin-related hyperpigmentation disorders, the plant Dalea elegans was submitted to fractionation with the aim of obtaining its anti-tyrosinase principle. Bioguided fractionation of D. elegans led to the isolation of 5,2',4...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.04.025

    authors： Chiari ME,Vera DM,Palacios SM,Carpinella MC

    更新日期：2011-06-01 00:00:00

  • Doxifluridine-conjugated 2-5A analog shows strong RNase L activation ability and tumor suppressive effect.

    abstract：:RNase L is activated by 2',5'-oligoadenylates (2-5A) at subnanomolar levels to cleave single-stranded RNA. We previously reported the hypothesis that the introduction of an 8-methyladenosine residue at the 2'-terminus of the 2-5A tetramer shifts the 2-5A binding site of RNase L. In this study, we synthesized various 5...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.06.033

    authors： Kitamura Y,Kito S,Nakashima R,Tanaka K,Nagaoka K,Kitade Y

    更新日期：2016-08-15 00:00:00

  • Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa.

    abstract：:A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene sub...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.12.019

    authors： Kochanny MJ,Adler M,Ewing J,Griedel BD,Ho E,Karanjawala R,Lee W,Lentz D,Liang AM,Morrissey MM,Phillips GB,Post J,Sacchi KL,Sakata ST,Subramanyam B,Vergona R,Walters J,White KA,Whitlow M,Ye B,Zhao Z,Shaw KJ

    更新日期：2007-03-01 00:00:00

  • Acidic biphenyl derivatives: synthesis and biological activity of a new series of potent 5-HT(4) receptor antagonists.

    abstract：:Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin mediates a positive chronotropic and inotropic response through 5-HT4 receptors in the atrium and ventricle of the heart. Recent investigations have revealed in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.09.004

    authors： Brudeli B,Andressen KW,Moltzau LR,Nilsen NO,Levy FO,Klaveness J

    更新日期：2013-11-15 00:00:00

  • A genetically selected cyclic peptide inhibitor of BCL6 homodimerization.

    abstract：:We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexapeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its h...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.03.012

    authors： Osher EL,Castillo F,Elumalai N,Waring MJ,Pairaudeau G,Tavassoli A

    更新日期：2018-07-15 00:00:00

  • Chiral switch of enzymatic ketone reduction by addition of gamma-cyclodextrin.

    abstract：:We report a chiral switch in the configuration of 1-(p-methoxyphenyl)-propan-2-ol, synthesized in aqueous media by ketoreductase in the presence of high concentration of gamma-CD. NMR, ECD and fluorescence spectrometry were used in the effort to explain this unexpected effect. A comparison has been made between the ca...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.07.070

    authors： Petkova GA,Král V

    更新日期：2010-09-15 00:00:00

  • A study on the conversion of indanones into carbostyrils.

    abstract：:We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrang...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00116-0

    authors： Torisawa Y,Nishi T,Minamikawa Ji

    更新日期：2003-05-15 00:00:00

  • Synthesis and biological evaluation of nonpeptide mimetics of omega-conotoxin GVIA.

    abstract：:A benzothiazole-derived compound (4a) designed to mimic the C(alpha)-C(beta) bond vectors and terminal functionalities of Lys2, Tyr13 and Arg17 in omega-conotoxin GVIA was synthesised, together with analogues (4b-d), which had each side-chain mimic systematically truncated or eliminated. The affinity of these compound...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.05.040

    authors： Baell JB,Duggan PJ,Forsyth SA,Lewis RJ,Lok YP,Schroeder CI

    更新日期：2004-08-01 00:00:00

  • A new dihydroxanthenone from a plant-associated strain of the fungus Chaetomium globosum demonstrates anticancer activity.

    abstract：:Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain, Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone, globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new xantho...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.07.048

    authors： Wijeratne EM,Turbyville TJ,Fritz A,Whitesell L,Gunatilaka AA

    更新日期：2006-12-01 00:00:00