Design and synthesis of 1-aminocycloalkane-1-carboxylic acid-substituted deltorphin analogues: unique delta and mu opioid activity in modified peptides.

Abstract:

:Deltorphin analogues were substituted by a series of achiral C alpha,alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carboxylic acids, Ac chi c, where chi = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in deltorphin C, and in position 2 in [Ac6c2,-des-Phe3]deltorphin C hexapeptide. Receptor assays indicated that even though Ac6c2 and Ac6c3 exhibited a diminished Ki delta by ca. 20-fold (2.5-3.3 nM) relative to deltorphin C (Ki delta = 0.15 nM), selectivity was marginally elevated (Ki mu/Ki delta = 1250) or enhanced by about 70%, and both peptides fitted stringent iterative calculations for a two-site binding model (eta = 0.625 and 0.766, respectively, P < 0.0001). The disubstituted [Ac6c2,3]- or [Ac6c2,des-Phe3]deltorphin analogues yielded peptides with decreased Ki delta, such that the latter peptide was essentially inactive. The presence of Ac5c or Ac3c in place of Phe3 further diminished Ki delta (15.4 to 19.0 nM), yet delta selectivity only fell about one-half (Ki mu/Ki delta = 440 and 535, respectively), and only the former peptide fitted a two-site binding model (eta = 0.799). The replacement of Asp4 by Ac6c, Ac5c, or Ac3c produced essentially nonselective analogues through the acquisition of high mu affinities (2.5, 0.58 and 0.27 nM, respectively) while maintaining high delta affinities (Ki delta = 0.045-0.054 nM) which were about 3-fold greater than that of deltorphin C. Using pharmacological assays in vitro (mouse vas deferens and guinea pig ileum), position 3-substituted analogues all indicated substantial losses in bioactivity, whereas substitution by 1-aminocycloalkanes at the fourth position retained high delta activity. In fact, the bioactivity of [Ac3c4]deltorphin C indicated a peptide with relatively weak delta selectivity, which was comparable to the observations with the receptor binding data. In summary, the data confirmed that (i) delta selectivity occurs in the absence of D-chirality at position 2, (ii) the aromaticity of Phe3 is replaceable by an achiral residue with a hydrophobic ring-saturated side chain, and (iii) the acquisition of dual high-affinity analogues occurs through the elimination of the anionic function at position 4 and replacement by an amino acid with a hydrophobic side chain.

journal_name

J Med Chem

authors

Breveglieri A,Guerrini R,Salvadori S,Bianchi C,Bryant SD,Attila M,Lazarus LH

doi

10.1021/jm950490j

subject

Has Abstract

pub_date

1996-02-02 00:00:00

pages

773-80

issue

3

eissn

0022-2623

issn

1520-4804

pii

jm950490j

journal_volume

39

pub_type

杂志文章
  • Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins.

    abstract::A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.8b00010

    authors: D de Araujo A,Lim J,Wu KC,Xiang Y,Good AC,Skerlj R,Fairlie DP

    更新日期:2018-04-12 00:00:00

  • 7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics. 2. Pharmacological profile of 7-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-piperidin-1-yl]propoxy]-3-(hydroxymeth yl)chromen -4-one (abaperidone, FI-8602).

    abstract::A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for D2 receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypica...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm9810396

    authors: Bolós J,Anglada L,Gubert S,Planas JM,Agut J,Príncep M,De la Fuente N,Sacristán A,Ortiz JA

    更新日期:1998-12-31 00:00:00

  • Use of medium-sized cycloalkyl rings to enhance secondary binding: discovery of a new class of human immunodeficiency virus (HIV) protease inhibitors.

    abstract::A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00011a008

    authors: Romines KR,Watenpaugh KD,Tomich PK,Howe WJ,Morris JK,Lovasz KD,Mulichak AM,Finzel BC,Lynn JC,Horng MM

    更新日期:1995-05-26 00:00:00

  • Design, synthesis, and evaluation of oxygen-containing macrocyclic peptidomimetics as inhibitors of HCV NS3 protease.

    abstract::HCV infection is considered a silent epidemic because most people infected do not develop acute symptoms. Instead, the disease progresses to a chronic state leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat this major health threat. The HCV NS3 serine protease has been the target of contin...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm801201u

    authors: Velázquez F,Venkatraman S,Blackman M,Pinto P,Bogen S,Sannigrahi M,Chen K,Pichardo J,Hart A,Tong X,Girijavallabhan V,Njoroge FG

    更新日期:2009-02-12 00:00:00

  • Design, chemical synthesis, and biological evaluation of thiosaccharide analogues of morphine- and codeine-6-glucuronide.

    abstract::A series of 6-beta-thiosaccharide analogues of morphine-6-glucuronide (M6G) and codeine-6-glucuronide (C6G) were synthesized and evaluated with the objective of preparing an analogue of M6G with improved biological activity. The affinity of the thiosaccharide analogues of M6G and C6G was examined by competitive bindin...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm049554t

    authors: MacDougall JM,Zhang XD,Polgar WE,Khroyan TV,Toll L,Cashman JR

    更新日期:2004-11-04 00:00:00

  • Molecular model of the alpha(IIb)beta(3) integrin.

    abstract::A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm030146j

    authors: Feuston BP,Culberson JC,Hartman GD

    更新日期:2003-12-04 00:00:00

  • Design, Synthesis, and Activity Study of Water-Soluble, Rapid-Release Propofol Prodrugs.

    abstract::In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma w...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00698

    authors: Liu LQ,Hong PX,Song XH,Zhou CC,Ling R,Kang Y,Qi QR,Yang J

    更新日期:2020-07-23 00:00:00

  • The synthesis of nucleoside 5'-O-(1,1-dithiotriphosphates).

    abstract::Appropriately protected nucleoside 5'-O-(2-thio-1,3,2-dithiaphospholanes) react with inorganic pyrophosphate in the presence of a strong base catalyst (DBU) to give nucleoside 5'-O-(1,1-dithiotriphosphates) 1a-g. The latter compounds, including an AZT analogue, show modest antivirial activity against HIV-1 and HIV-2 r...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00048a021

    authors: Okruszek A,Olesiak M,Balzarini J

    更新日期:1994-10-28 00:00:00

  • Structural studies of metyrapone: a potent inhibitor of cytochrome P-450.

    abstract::The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00363a008

    authors: Rossi M

    更新日期:1983-09-01 00:00:00

  • Synthesis and biological evaluation of a fluorine-18 derivative of dasatinib.

    abstract::Tyrosine kinases often play pivotal roles in the pathogenesis of cancer and are good candidates for therapeutic intervention and targeted molecular imaging. The precursor synthesis, radiosynthesis, and biological characterization of a fluorine-18 analog of dasatinib, a multitargeted kinase inhibitor, are reported. Com...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm070342g

    authors: Veach DR,Namavari M,Pillarsetty N,Santos EB,Beresten-Kochetkov T,Lambek C,Punzalan BJ,Antczak C,Smith-Jones PM,Djaballah H,Clarkson B,Larson SM

    更新日期:2007-11-15 00:00:00

  • Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones.

    abstract::A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation. ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00373a015

    authors: Heeres J,Backx LJ,Van Cutsem J

    更新日期:1984-07-01 00:00:00

  • Methylation of Daptomycin Leading to the Discovery of Kynomycin, a Cyclic Lipodepsipeptide Active against Resistant Pathogens.

    abstract::Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin co...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.9b01957

    authors: Chow HY,Po KHL,Gao P,Blasco P,Wang X,Li C,Ye L,Jin K,Chen K,Chan EWC,You X,Yi Tsun Kao R,Chen S,Li X

    更新日期:2020-03-26 00:00:00

  • Design and Synthesis of Potent and Highly Selective Orexin 1 Receptor Antagonists with a Morphinan Skeleton and Their Pharmacologies.

    abstract::Nalfurafine, a κ-selective opioid receptor agonist, unexpectedly showed a selective antagonist activity toward the orexin 1 receptor (OX1R) (Ki = 250 nM). Modification of the 17-amino side chain of the opioid ligand to an arylsulfonyl group and the 6-furan acrylamide chain to 2-pyridyl acrylamide led to compound 71 wi...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.6b01418

    authors: Nagase H,Yamamoto N,Yata M,Ohrui S,Okada T,Saitoh T,Kutsumura N,Nagumo Y,Irukayama-Tomobe Y,Ishikawa Y,Ogawa Y,Hirayama S,Kuroda D,Watanabe Y,Gouda H,Yanagisawa M

    更新日期:2017-02-09 00:00:00

  • Biological and biophysical properties of the histone deacetylase inhibitor suberoylanilide hydroxamic acid are affected by the presence of short alkyl groups on the phenyl ring.

    abstract::Inhibition of histone deacetylases (HDACs) leads to growth arrest, differentiation, or apoptosis of tumor cell lines, suggesting HDACs as promising targets for cancer therapy. At present, only one HDAC inhibitor (HDACi) is used in therapy: suberoylanilide hydroxamic acid (SAHA). Here, we describe the synthesis and bio...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm901561u

    authors: Oger F,Lecorgne A,Sala E,Nardese V,Demay F,Chevance S,Desravines DC,Aleksandrova N,Le Guével R,Lorenzi S,Beccari AR,Barath P,Hart DJ,Bondon A,Carettoni D,Simonneaux G,Salbert G

    更新日期:2010-03-11 00:00:00

  • Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.

    abstract::Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm0601001

    authors: Sheppard GS,Wang J,Kawai M,Fidanze SD,BaMaung NY,Erickson SA,Barnes DM,Tedrow JS,Kolaczkowski L,Vasudevan A,Park DC,Wang GT,Sanders WJ,Mantei RA,Palazzo F,Tucker-Garcia L,Lou P,Zhang Q,Park CH,Kim KH,Petros A,Ol

    更新日期:2006-06-29 00:00:00

  • 4-Methyl-3-(arylsulfonyl)furoxans: a new class of potent inhibitors of platelet aggregation.

    abstract::A series of 4-methyl-3-(arylthio)furoxans were synthesized by oxidation of 1-(arylthio)-2-methylglyoxymes with dinitrogen tetroxide. Reduction with trimethyl phosphite of the furoxan derivatives afforded the corresponding furazans, while oxidation with an equimolar amount of 30% hydrogen peroxide in acetic acid or wit...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00095a028

    authors: Calvino R,Fruttero R,Ghigo D,Bosia A,Pescarmona GP,Gasco A

    更新日期:1992-08-21 00:00:00

  • Anticancer and antimalarial efficacy and safety of artemisinin-derived trioxane dimers in rodents.

    abstract::In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2)...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm0303711

    authors: Posner GH,McRiner AJ,Paik IH,Sur S,Borstnik K,Xie S,Shapiro TA,Alagbala A,Foster B

    更新日期:2004-02-26 00:00:00

  • Design, synthesis, and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli.

    abstract::Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm970414b

    authors: Chen S,Lin CH,Kwon DS,Walsh CT,Coward JK

    更新日期:1997-11-07 00:00:00

  • Synthesis, structure-activity relationships, and antitumor studies of 2-benzoxazolyl hydrazones derived from alpha-(N)-acyl heteroaromatics.

    abstract::Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized. T...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm060232u

    authors: Easmon J,Pürstinger G,Thies KS,Heinisch G,Hofmann J

    更新日期:2006-10-19 00:00:00

  • (3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine:D-alanine ligase.

    abstract::The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesi...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00128a033

    authors: Chakravarty PK,Greenlee WJ,Parsons WH,Patchett AA,Combs P,Roth A,Busch RD,Mellin TN

    更新日期:1989-08-01 00:00:00

  • Isosorbide-2-benzyl carbamate-5-salicylate, a peripheral anionic site binding subnanomolar selective butyrylcholinesterase inhibitor.

    abstract::Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm9014845

    authors: Carolan CG,Dillon GP,Khan D,Ryder SA,Gaynor JM,Reidy S,Marquez JF,Jones M,Holland V,Gilmer JF

    更新日期:2010-02-11 00:00:00

  • Protoberberine alkaloids as antimalarials.

    abstract::The protoberberine alkaloids berberine (1), palmatine (2), jatrorrhizine (3), and several berberine derivatives (4-10) were tested for antimalarial activity in vitro against Plasmodium falciparum and in vivo against Plasmodium berghei. The berberine derivatives 4-10 were designed and synthesized to maximize structural...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00401a006

    authors: Vennerstrom JL,Klayman DL

    更新日期:1988-06-01 00:00:00

  • Novel glucocorticoid antedrugs possessing a 17beta-(gamma-lactone) ring.

    abstract::The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm001035c

    authors: Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

    更新日期:2001-02-15 00:00:00

  • Targeted polysaccharide nanoparticle for adamplatin prodrug delivery.

    abstract::A series of conjugated hyaluronic acid particles (HAP), composed of a hydrophobic anticancer drug core and hydrophilic cyclodextrin/hyaluronic acid shell, were prepared through self-assembling and characterized by (1)H NMR titration, electron microscopy, zeta potential, and dynamic light-scattering experiments. The na...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm4014168

    authors: Yang Y,Zhang YM,Chen Y,Chen JT,Liu Y

    更新日期:2013-12-12 00:00:00

  • Adrenoceptor blocking agents. Compounds related to metoprolol.

    abstract::A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00136a014

    authors: Lövgren K,Hedberg A,Nilsson JL

    更新日期:1981-04-01 00:00:00

  • Rapid identification of ligand-binding sites by using an assignment-free NMR approach.

    abstract::In this study, we developed an assignment-free approach for rapid identification of ligand-binding sites in target proteins by using NMR. With a sophisticated cell-free stable isotope-labeling procedure that introduces (15)N- or (13)C-labels to specific atoms of target proteins, this approach requires only a single se...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm4014357

    authors: Kodama Y,Takeuchi K,Shimba N,Ishikawa K,Suzuki E,Shimada I,Takahashi H

    更新日期:2013-11-27 00:00:00

  • Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method.

    abstract::AFTIR (after flowing through immobilized receptor) is a novel method for screening herbal extracts for pharmaceutical properties. Using AFTIR, we identified Cynarin in Echinacea purpurea by its selective binding to chip immobilized CD28, a receptor of T-cells, which is instrumental to immune functioning. The results o...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm0509039

    authors: Dong GC,Chuang PH,Forrest MD,Lin YC,Chen HM

    更新日期:2006-03-23 00:00:00

  • Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).

    abstract::Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design and synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ERα competitively (IC5...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.6b00753

    authors: Liu J,Zheng S,Akerstrom VL,Yuan C,Ma Y,Zhong Q,Zhang C,Zhang Q,Guo S,Ma P,Skripnikova EV,Bratton MR,Pannuti A,Miele L,Wiese TE,Wang G

    更新日期:2016-09-08 00:00:00

  • (-)-Arctigenin as a lead structure for inhibitors of human immunodeficiency virus type-1 integrase.

    abstract::The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm950387u

    authors: Eich E,Pertz H,Kaloga M,Schulz J,Fesen MR,Mazumder A,Pommier Y

    更新日期:1996-01-05 00:00:00

  • Synthesis of peptide analogues of prothrombin precursor sequence 5-9. Substrate specificity of vitamin K dependent carboxylase.

    abstract::Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00138a013

    authors: Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

    更新日期:1981-06-01 00:00:00