当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > Lipid bilayer partitioning and stability of camptothecin drugs.

Lipid bilayer partitioning and stability of camptothecin drugs.

Abstract：

:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to determine (1) the structural basis of drug binding to lipid bilayers, (2) the lipid bilayer stability of each drug's alpha-hydroxylactone moiety, a pharmacophore which is essential for antitumor activity, and (3) the site of drug binding in the bilayer. Equilibrium affinities of camptothecin and related congeners for small unilamellar vesicles composed of electroneutral dimyristoylphosphatidylcholine (DMPC) or negatively-charged dimyristoylphosphatidylglycerol (DMPG) were determined using the method of fluorescence anisotropy titration. Experiments were conducted in phosphate-buffered saline (PBS) at 37 degrees C and overall association constants (K values) were determined. Of the seven compounds studied, the new compound 9-chloro-10,11-methylenedioxy-(20S)-camptothecin (CMC) was found to display the highest membrane affinities (KDMPC = 400 M-1, KDMPG = 320 M-1), followed by 10,11-methylenedioxy-camptothecin and camptothecin, which exhibited KDMPC and KDMPG values of 100 M-1 or greater. Topotecan displayed markedly reduced binding to lipid bilayers (KDMPC = 10 M-1, KDMPG = 50 M-1). HPLC assays were subsequently employed to assess the relative stabilities of the lactone ring of membrane-bound drugs. Our results clearly indicate that lipid bilayer interactions stabilize the lactone moiety of camptothecin drugs. In comparison to half-lives in PBS (37 degrees C) of 17 and 19 min for camptothecin and CMC, respectively, DMPC- or DMPG-bound drugs were found to be stable even for periods up to 72 h. Iodide quenching data indicate that membrane-bound camptothecin intercalates between the lipid acyl chains, in a protected environment well removed from the aqueous interface. In this manner lipid bilayer interactions stabilize the lactone ring structure of camptothecins and thereby conserve the biologically active form of each medication.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Burke TG,Mishra AK,Wani MC,Wall ME

doi

10.1021/bi00071a010

subject

Has Abstract

pub_date

1993-05-25 00:00:00

pages

5352-64

issue

20

eissn

0006-2960

issn

1520-4995

journal_volume

32

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全
  • Copurification of the FpvA ferric pyoverdin receptor of Pseudomonas aeruginosa with its iron-free ligand: implications for siderophore-mediated iron transport.

    abstract：:The Pseudomonas aeruginosa FpvA receptor is a TonB-dependent outer membrane transport protein that catalyzes uptake of ferric pyoverdin across the outer membrane. Surprisingly, FpvA expressed in P. aeruginosa grown in an iron-deficient medium copurifies with a ligand X that we have characterized by UV, fluorescence, a...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi990421x

    authors： Schalk IJ,Kyslik P,Prome D,van Dorsselaer A,Poole K,Abdallah MA,Pattus F

    更新日期：1999-07-20 00:00:00

  • Directed evolution of the suicide protein O⁶-alkylguanine-DNA alkyltransferase for increased reactivity results in an alkylated protein with exceptional stability.

    abstract：:Here we present a biophysical, structural, and computational analysis of the directed evolution of the human DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (hAGT) into SNAP-tag, a self-labeling protein tag. Evolution of hAGT led not only to increased protein activity but also to higher stability, especially...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi2016537

    authors： Mollwitz B,Brunk E,Schmitt S,Pojer F,Bannwarth M,Schiltz M,Rothlisberger U,Johnsson K

    更新日期：2012-02-07 00:00:00

  • Reversible transition between the surface trimer and membrane-inserted monomer of annexin 12.

    abstract：:Under mildly acidic conditions, annexin 12 (ANX) inserts into lipid membranes to form a transbilayer pore [Langen, R., et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 14060]. In this study, we have addressed the question of the oligomeric state of ANX in this transbilayer conformation by means of Forster-type resonanc...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi047805u

    authors： Ladokhin AS,Haigler HT

    更新日期：2005-03-08 00:00:00

  • Order and dynamics in mixtures of membrane glucolipids from Acholeplasma laidlawii studied by 2H NMR.

    abstract：:The two dominant glucolipids in Acholeplasma laidlawii, viz., 1,2-diacyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerol (MGlcDG) and 1,2-diacyl-3-O-[alpha-D-glucopyranosyl-(1----2)-O-alpha-D-glucopyranosyl ]- sn-glycerol (DGlcDG), have markedly different phase behavior. MGlcDG has an ability to form nonlamellar phases, wher...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00234a012

    authors： Eriksson PO,Rilfors L,Wieslander A,Lundberg A,Lindblom G

    更新日期：1991-05-21 00:00:00

  • Phosphoryl transfer between phosphorylated histidine-containing protein and histidine-containing protein is not autocatalytic.

    abstract：:Histidine-containing protein, HPr, is a phosphocarrier protein that is part of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated by enzyme I, and P-HPr transfers the phosphoryl group to the IIA domain of a number of sugar-specific enzyme II complexes. Autocatalytic phosphoryl tra...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00073a025

    authors： Anderson JW,Waygood EB

    更新日期：1993-06-08 00:00:00

  • Stimulation of transcript elongation requires both the zinc finger and RNA polymerase II binding domains of human TFIIS.

    abstract：:The eukaryotic transcriptional factor TFIIS enhances transcript elongation by RNA polymerase II. Here we describe two functional domains in the 280 amino acid human TFIIS protein: residues within positions 100-230 are required for binding to polymerase, and residues 230-280, which form a zinc finger, are required in c...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00245a026

    authors： Agarwal K,Baek KH,Jeon CJ,Miyamoto K,Ueno A,Yoon HS

    更新日期：1991-08-06 00:00:00

  • Molecular structure of rat brain apamin receptor: differential photoaffinity labeling of putative K+ channel subunits and target size analysis.

    abstract：:Two photoreactive apamin derivatives were prepared with an aryl azide [[(azidonitrophenyl)amino]acetate (ANPAA)] group coupled at different positions on the neurotoxin molecule. These ligands were used to identify membrane components in the environment of the neuronal binding site that is associated with a Ca2+-activa...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00362a010

    authors： Seagar MJ,Labbé-Jullié C,Granier C,Goll A,Glossmann H,Van Rietschoten J,Couraud F

    更新日期：1986-07-15 00:00:00

  • An unusual catalytic subunit for the cAMP-dependent protein kinase of Dictyostelium discoideum.

    abstract：:The cAMP-dependent protein kinase (cAPK) plays an essential role during differentiation and fruit morphogenesis in Dictyostelium discoideum. The presence of an open reading frame on the gene, pkaC (previously named either Dd PK2 or Dd PK3 by different groups), predicts a 73-kDa polypeptide with 54% similarity to the c...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00088a003

    authors： Anjard C,Etchebehere L,Pinaud S,Véron M,Reymond CD

    更新日期：1993-09-21 00:00:00

  • Rapid Oxidation Following Photoreduction in the Avian Cryptochrome4 Photocycle.

    abstract：:Avian magnetoreception is assumed to occur in the retina. Although its molecular mechanism is unclear, magnetic field-dependent formation and the stability of radical-containing photointermediate(s) are suggested to play key roles in a hypothesis called the radical pair mechanism. Chicken cryptochrome4 (cCRY4) has bee...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.0c00495

    authors： Otsuka H,Mitsui H,Miura K,Okano K,Imamoto Y,Okano T

    更新日期：2020-09-29 00:00:00

  • Intrinsic uncoupling in proton-pumping cytochrome c oxidase: pH dependence of cytochrome c oxidation in coupled and uncoupled phospholipid vesicles.

    abstract：:The pH dependence of the transient aerobic kinetics of cytochromes c and a has been investigated with cytochrome oxidase reconstituted in phospholipid vesicles in the absence and presence of an uncoupler and an ionophore. The cytochrome a reduction level immediately after the burst phase was 60-80% and was not signifi...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00434a007

    authors： Maison-Peteri B,Malmström BG

    更新日期：1989-04-18 00:00:00

  • Small Molecule Rescue and Glycosidic Conformational Analysis of the Twister Ribozyme.

    abstract：:The number of self-cleaving ribozymes has increased sharply in recent years, giving rise to elaborations of the four known ribozyme catalytic strategies, α, β, γ, and δ. One such extension is utilized by the twister ribozyme, which is hypothesized to conduct δ, or general acid catalysis, via N3 of the syn adenine +1 n...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.9b00742

    authors： Messina KJ,Kierzek R,Tracey MA,Bevilacqua PC

    更新日期：2019-12-03 00:00:00

  • A high-affinity fluorenone-based beta 2-adrenergic receptor antagonist with a photoactivatable pharmacophore.

    abstract：:To develop molecules capable of directly probing the catechol binding region of the beta(2)-adrenergic receptor (beta(2)AR), novel benzophenone- and fluorenone-based beta(2)AR antagonists were prepared as potential photoaffinity probes. While the benzophenone-containing ligands bound with relatively modest affinity, o...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi001342k

    authors： Wu Z,Ruoho AE

    更新日期：2000-10-24 00:00:00

  • Acquisition of an insertion peptide for efficient aminoacylation by a halophile tRNA synthetase.

    abstract：:Enzymes of halophilic organisms contain unusual peptide motifs that are absent from their mesophilic counterparts. The functions of these halophile-specific peptides are largely unknown. Here we have identified an unusual peptide that is unique to several halophile archaeal cysteinyl-tRNA synthetases (CysRS), which ca...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi0521386

    authors： Evilia C,Hou YM

    更新日期：2006-06-06 00:00:00

  • DNAzyme-mediated silencing of ornithine decarboxylase.

    abstract：:The value of reducing the activity of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is well-appreciated. Polyamines are necessary components for cell growth, and manipulation of polyamine homeostasis may be an effective strategy for the treatment of a number of disorders, including neo...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi047918d

    authors： Ackermann JM,Kanugula S,Pegg AE

    更新日期：2005-02-15 00:00:00

  • Either the carboxyl- or the amino-terminal region of the human ecto-ATPase (E-NTPDase 2) confers detergent and temperature sensitivity to the chicken ecto-ATP-diphosphohydrolase (E-NTPDase 8).

    abstract：:Human ecto-ATPase (E-NTPDase 2) and chicken ecto-ATP-diphosphohydrolase (E-NTPDase 8) are cell surface nucleotidases with two transmembranous domains, one each at the N- and C-termini. Hydrolysis of substrates occurs in active sites residing in their extracellular domains. Human ecto-ATPase activity is decreased by NP...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi050019k

    authors： Mukasa T,Lee Y,Knowles AF

    更新日期：2005-08-23 00:00:00

  • Acylation of myelin basic protein peptide 1-21 with alkyl carboxylates 2-10 carbons long affects secondary structure and posttranslational modification.

    abstract：:A peptide consisting of the first 21 residues of human myelin basic protein (MBP) was synthesized. The N-terminal alanine of portions was blocked in separate experiments with alkyl carboxylates varying in size from 2 to 10 carbon atoms. The effects of these different alkyl carboxylates at the N-terminus on the seconda...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00180a008

    authors： Costentino M,Pritzker L,Boulias C,Moscarello MA

    更新日期：1994-04-12 00:00:00

  • Escherichia coli ATP synthase alpha subunit Arg-376: the catalytic site arginine does not participate in the hydrolysis/synthesis reaction but is required for promotion to the steady state.

    abstract：:The three catalytic sites of the F(O)F(1) ATP synthase interact through a cooperative mechanism that is required for the promotion of catalysis. Replacement of the conserved alpha subunit Arg-376 in the Escherichia coli F(1) catalytic site with Ala or Lys resulted in turnover rates of ATP hydrolysis that were 2 x 10(3...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi992530h

    authors： Le NP,Omote H,Wada Y,Al-Shawi MK,Nakamoto RK,Futai M

    更新日期：2000-03-14 00:00:00

  • DCCD inhibits the reactions of the iron-sulfur protein in Rhodobacter sphaeroides chromatophores.

    abstract：:N,N'-dicyclohexylcarbodiimide (DCCD) has been reported to inhibit proton translocation by cytochrome bc(1) and b(6)f complexes without significantly altering the rate of electron transport, a process referred to as decoupling. To understand the possible role of DCCD in inhibiting the protonogenic reactions of cytochro...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi001482u

    authors： Shinkarev VP,Ugulava NB,Crofts AR,Wraight CA

    更新日期：2000-12-26 00:00:00

  • Crystal structure of adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.

    abstract：:Adenosine 5'-phosphosulfate (APS) kinase catalyzes the second reaction in the two-step conversion of inorganic sulfate to 3'-phosphoadenosine 5'-phosphosulfate (PAPS). This report presents the 2.0 A resolution crystal structure of ligand-free APS kinase from the filamentous fungus, Penicillium chrysogenum. The enzyme ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi9924157

    authors： MacRae IJ,Segel IH,Fisher AJ

    更新日期：2000-02-22 00:00:00

  • Covalent linkage of phospholipid to myelin basic protein: identification of serine-54 as the site of attachment.

    abstract：:The peptide portion of the lipopeptide isolated from bovine myelin basic protein contained glycine, lysine, and serine in a 2:1:1 molar ratio as determined by amino acid analysis. The N-terminus of the peptide was determined to be glycine. The tetrapeptide Gly53-Ser-Gly-Lys56 was the only segment of myelin basic prote...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00357a059

    authors： Chang PC,Yang JC,Fujitaki JM,Chiu KC,Smith RA

    更新日期：1986-05-06 00:00:00

  • Role of guanine nucleotides in the vinblastine-induced self-association of tubulin: effects of guanosine alpha,beta-methylenetriphosphate and guanosine alpha,beta-methylenediphosphate.

    abstract：:It is now well established that guanine nucleotides are allosteric effectors of the vinca alkaloid-induced self-association of tubulin. GDP enhances self-association for vinblastine-, vincristine- and vinorelbine-induced spiral assembly relative to GTP by 0.90 +/- 0.17 kcal/mol [Lobert et al. (1996) Biochemistry 35, 6...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi971120v

    authors： Vulevic B,Lobert S,Correia JJ

    更新日期：1997-10-21 00:00:00

  • The three-dimensional structure of the gallium complex of azoverdin, a siderophore of Azomonas macrocytogenes ATCC 12334, determined by NMR using residual dipolar coupling constants.

    abstract：:In iron-deficient conditions, Azomonas macrocytogenes ATCC 12334 excretes a fluorescent siderophore called azoverdin, which is composed of a six-amino-acid peptide chain linked to a chromophore. Azoverdin chelates iron(III) very strongly, solubilizing it and transporting it back into the cells using an outer-membrane ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi025990a

    authors： Wasielewski E,Atkinson RA,Abdallah MA,Kieffer B

    更新日期：2002-10-15 00:00:00

  • Evolutionary optimization of the catalytic effectiveness of an enzyme.

    abstract：:The kinetic and thermodynamic features of reactions catalyzed by present-day enzymes appear to be the consequence of the evolution of these proteins toward maximal catalytic effectiveness. These features are identified and analyzed (in detail for one substrate-one product enzymes) by using ideas that link the energeti...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00450a009

    authors： Burbaum JJ,Raines RT,Albery WJ,Knowles JR

    更新日期：1989-11-28 00:00:00

  • Amino acid sequence of ragweed allergen Ra3.

    abstract：:The complete amino acid sequence of ragweed pollen allergen Ra3 has been determined. The molecule consists of 101 amino acid residues and to date is the only allergen isolated from Ambrosia elatior (short ragweed) which contains carbohydrate. This particular preparation of allergen has a single, unique amino acid sequ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00566a010

    authors： Klapper DG,Goodfriend L,Capra JD

    更新日期：1980-12-09 00:00:00

  • Effect of reversed heme orientation on circular dichroism and cooperative oxygen binding of human adult hemoglobin.

    abstract：:We found that recombinant human adult hemoglobin (rHb A) expressed in Escherichia coli showed heterogeneity of components with the intensity of a positive CD band at 260 nm and that it could be resolved into three components (SP-1, SP-2, and SP-3) by SP-Sepharose column chromatography. 1H NMR revealed that SP-1 is ide...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi7015519

    authors： Nagai M,Nagai Y,Aki Y,Imai K,Wada Y,Nagatomo S,Yamamoto Y

    更新日期：2008-01-15 00:00:00

  • Site-directed mutagenesis and molecular modeling identify a crucial amino acid in specifying the heparin affinity of FGF-1.

    abstract：:Heparin potentiates the mitogenic activity of FGF-1 by increasing the affinity for its receptor and by extending its biological half-life. During the course of labeling human FGF-1 with Na(125)I and chloramine T, it was observed that the protein lost its ability to bind to heparin. In contrast, bovine FGF-1 retained i...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi9903345

    authors： Patrie KM,Botelho MJ,Franklin K,Chiu IM

    更新日期：1999-07-20 00:00:00

  • A family of leukemia inhibitory factor-binding peptides that can act as antagonists when conjugated to poly(ethylene glycol).

    abstract：:A panel of six naïve 14-residue random peptide libraries displayed polyvalently on M13 phage was pooled and sorted against human leukemia inhibitory factor (LIF). After four rounds of selection, a single large family of peptides with the consensus sequence XCXXXXG(A/S)(D/E)(W/F)WXCF was found to bind specifically to L...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi035303v

    authors： Fairlie WD,Uboldi AD,Hemmings GJ,Smith BJ,Martin HM,Morgan PO,Baca M

    更新日期：2003-11-18 00:00:00

  • Crystallographic structures of ribonuclease S variants with nonpolar substitution at position 13: packing and cavities.

    abstract：:Seven hydrophobic residues ranging in size from glycine to phenylalanine have been substituted for the wild-type methionine residue at position 13 in a 15-residue truncated version (S15) of S-peptide, the small component of ribonuclease S. Complexes of both S-15 and the seven variants with S-protein yielded isomorphou...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00164a005

    authors： Varadarajan R,Richards FM

    更新日期：1992-12-15 00:00:00

  • Determination of the rate and yield of B-side quinone reduction in Rhodobacter capsulatus reaction centers.

    abstract：:In the native purple bacterial reaction center (RC), light-driven charge separation utilizes only the A-side cofactors, with the symmetry related B-side inactive. The process is initiated by electron transfer from the excited primary donor (P*) to the A-side bacteriopheophytin (P* --> P+ H(A)-) in approximately 3 ps. ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi060277x

    authors： Kee HL,Laible PD,Bautista JA,Hanson DK,Holten D,Kirmaier C

    更新日期：2006-06-13 00:00:00

  • Analysis of substrate access to active sites in bacterial multicomponent monooxygenase hydroxylases: X-ray crystal structure of xenon-pressurized phenol hydroxylase from Pseudomonas sp. OX1.

    abstract：:In all structurally characterized bacterial multicomponent monooxygenase (BMM) hydroxylase proteins, a series of hydrophobic cavities in the α-subunit trace a conserved path from the protein exterior to the carboxylate-bridged diiron active site. This study examines these cavities as a potential route for transport of...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi201248b

    authors： McCormick MS,Lippard SJ

    更新日期：2011-12-27 00:00:00