Abstract:
:Drug molecules are typically hydrophobic and small in order to traverse membranes to reach cytoplasmic targets, but we have discovered that more polar molecules can be delivered across membranes using water-soluble, moderately hydrophobic membrane peptides of the pHLIP (pH low insertion peptide) family. Delivery of polar cargo molecules could expand the chemical landscape for pharmacological agents that have useful activity but are too polar by normal drug criteria. The spontaneous insertion and folding of the pHLIP peptide across a lipid bilayer seeks a free energy minimum, and insertion is accompanied by a release of energy that can be used to translocate cell-impermeable cargo molecules. In this study, we report our first attempt to tune the hydrophobicity of a polar cargo, phallacidin, in a systematic manner. We present the design, synthesis, and characterization of three phallacidin cargoes, where the hydrophobicity of the cargo was tuned by the attachment of diamines of various lengths of hydrophobic chains. The phallacidin cargoes were conjugated to pHLIP and shown to selectively inhibit the proliferation of cancer cells in a concentration-dependent manner at low pH.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Wijesinghe D,Engelman DM,Andreev OA,Reshetnyak YKdoi
10.1021/bi2009773subject
Has Abstractpub_date
2011-11-29 00:00:00pages
10215-22issue
47eissn
0006-2960issn
1520-4995journal_volume
50pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Carbon monoxide dehydrogenase (CODH) from Clostridium thermoaceticum plays a central role in the newly discovered acetyl-CoA pathway [Wood, H.G., Ragsdale, S.W., & Pezacka, E. (1986) FEMS Microbiol. Rev. 39, 345-362]. The enzyme catalyzes the formation of acetyl-CoA from methyl, carbonyl, and CoA groups, and it has sp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00417a045
更新日期:1988-08-23 00:00:00
abstract::Alpha2u-globulin is a male rat liver protein under multihormonal control which represents approximately 1% of hepatic protein synthesis. We have measured the rate of transcription of the alpha2u-globulin gene using a nuclear cell-free transcriptional system with mercurated CTP as substrate for the endogenous RNA polym...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00608a023
更新日期:1978-07-25 00:00:00
abstract::The dimeric two-component system transmitter protein NRII (NtrB) of Escherichia coli, product of glnL (ntrB), controls transcription of nitrogen-regulated genes by catalyzing the phosphorylation and dephosphorylation of the transcription factor NRI (NtrC). Previous studies showed that the PII signal transduction prote...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000794u
更新日期:2000-11-07 00:00:00
abstract::Carbamoyl phosphate synthetase from E. coli catalyzes the synthesis of carbamoyl phosphate through a series of four reactions occurring at three active sites connected by a molecular tunnel of 100 A. To understand the mechanism for coordination and synchronization among the active sites, the pre-steady-state time cour...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi992772h
更新日期:2000-05-02 00:00:00
abstract::Protein kinase C (PKC) interacted with phospholipid vesicles in a calcium-dependent manner and produced two forms of membrane-associated PKC: a reversibly bound form and a membrane-inserted form. The two forms of PKC were isolated and compared with respect to enzyme stability, cofactor requirements, and phorbol ester ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00420a003
更新日期:1988-10-04 00:00:00
abstract::Glycosylases specifically recognize and flip their target base out of the DNA helix into the enzyme's active site. Our simulations show that a partially flipped state, already present in free DNA carrying a T:G mispair, becomes the more probable state compared to the closed state after binding of thymine DNA glycosyla...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00409
更新日期:2018-10-02 00:00:00
abstract::For the study of the protein--protein and protein--nucleic acid interactions in the assembly of virus particles, laser Raman spectra have been obtained in H2O and D2O solutions and as a function of temperature for the following Salmonella phage P22 components: mature phage particles, isolated mature phage DNA, mature ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00259a023
更新日期:1982-08-03 00:00:00
abstract::Sphingosine, sphinganine, and other long-chain (sphingoid) bases inhibit protein kinase C in vitro and block cellular responses to agonists that are thought to act via this enzyme. To gain further insight into the mechanism of this inhibition, a series of long-chain analogues differing in alkyl chain length (11-20 car...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00434a004
更新日期:1989-04-18 00:00:00
abstract::In bacteria, regulatory phosphorylation of proteins at serine and/or threonine residues by Ser/Thr protein kinase (STPK) is an emerging theme in prokaryotic signaling, particularly since the prediction of the occurrence of several STPKs from genome sequencing and sequence surveys. Here we show that protein PknH posses...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035150b
更新日期:2003-12-30 00:00:00
abstract::This paper provides further characterization of a receptor that, in cells lacking the LDL receptor (FH fibroblasts), mediates lipoprotein binding, uptake, and degradation when incubated with oleate at concentrations not exceeding albumin binding capacity. This oleate-activated receptor is genetically distinct from the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00171a017
更新日期:1994-02-08 00:00:00
abstract::The structure of premature core enzyme, an obligatory intermediate in both in vivo and in vitro assembly of Escherichia coli DNA-dependent RNA polymerase, was compared with that of native core enzyme. Though this assembled but inactive form of core enzyme harbors the gross conformation similar to that of native enzyme...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00573a006
更新日期:1979-03-20 00:00:00
abstract::The diflavin reductases exemplified by mammalian cytochrome P450 reductase catalyze NADPH dehydrogenation and electron transfer to an associated monooxygenase. It has recently been proposed that double occupancy of the NADPH dehydrogenation site inhibits the NADPH to FAD hydride transfer step in this series of enzymes...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0360408
更新日期:2004-04-06 00:00:00
abstract::The effect of anions on the stability of different functional conformations of Hb is examined through the determination of the dependence of O(2) affinity on water activity (a(w)). The control of a(w) is effected by varying the sucrose osmolal concentration in the bathing solution according to the "osmotic stress" met...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9905361
更新日期:1999-09-07 00:00:00
abstract::The phosphorelay signal transduction pathway controls sporulation initiation in Bacillus subtilis. Transfer of a phosphoryl group from multiple kinases (KinA and KinB) through a single domain response regulator homologue (Spo0F), a phosphotransferase (Spo0B), and ultimately to a transcriptional regulator, (Spo0A) acti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981340o
更新日期:1998-11-24 00:00:00
abstract::Pairing rules have been developed to predict the sequence specificity of minor groove binding polyamides containing pyrrole (Py) and imidazole (Im) amino acids. An Im/Py pair distinguishes G.C from C.G and both of these from A.T/T.A base pairs. A Py/Py pair appears not to distinguish A.T from T.A base pairs. To test t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960744i
更新日期:1996-09-24 00:00:00
abstract::Our recently reported pressure-jump relaxation kinetics experiments on staphylococcal nuclease folding and unfolding [Vidugiris et al. (1995) Biochemistry 34, 4909] demonstrated that both transitions exhibit positive activation volumes, with that of folding being much larger than that of unfolding. Thus high pressure ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952012g
更新日期:1996-03-26 00:00:00
abstract::The effect of the general anesthetics alpha-chloralose and chloral hydrate as well as the nonanesthetic beta-chloralose on the order of phosphatidylcholine and phosphatidylcholine-cholesterol liposomes has been examined by 2H nuclear magnetic resonance. Chloral hydrate interacts with the hydrophilic head-group region,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00346a019
更新日期:1985-12-03 00:00:00
abstract::The trifunctional dinuclear platinum compounds 1,2/c,c [[cis-PtCl(NH(3))(2)]mu-H(2)N(CH(2))(6)NH(2)[cis-PtCl(2)(NH(3))]](+) and 1,2/t,c [[trans-PtCl(NH(3))(2)]mu-H(2)N(CH(2))(6)NH(2)[cis-PtCl(2)(NH(3))]](+) contain a monofunctional platinum coordination sphere linked to a cis-[PtCl(2)(amine)(2)] moiety. The compounds ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi030243e
更新日期:2004-06-22 00:00:00
abstract::The aromatic hydroxylation of six pairs of selectively deuterated monosubstituted benzenes was investigated with rat liver microsomes of various induction states. The substrates studied included 3,5-D2C6H3X (1a-6a) and 2,4,6-D3C6H2X (1b-6b), where X = Br, CN, NO2, OCH3, CH3, or Ph, respectively. The deuterium content ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00308a031
更新日期:1984-06-19 00:00:00
abstract::After borohydride reduction, carboxymethylation, and tryptic digestion of the holoenzyme of pig heart alanine aminotransferase, a single icosapeptide containing the N6-(phosphopyridoxyl)lysine residue was isolated by a combination of gel filtration and ion-exchange chromatogrpahy. Its primary structure was determined ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00581a015
更新日期:1979-07-10 00:00:00
abstract::Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are small enzymes that are ubiquitous in many organisms. They are important in biological processes such as cell proliferation, adhesion, migration, and invasiveness. LMW-PTP is expressed in mammalian cells as two isoforms (IF1 and IF2) originating through ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0620858
更新日期:2007-05-29 00:00:00
abstract::An empirical preduction algorithm which uses information on the shrs on either side) interactions in 20 proteins to assign every residue in a protein to one of five conformational states is described. The conformational states are defined in terms of the backbone dihedral angles of the residue so that the prediction a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00668a030
更新日期:1976-11-16 00:00:00
abstract::The biosynthesis of osteocalcin (OC), a bone-specific, noncollagenous protein, is stringently regulated during differentiation of the osteoblast phenotype. Glucocorticoids, and also 1,25(OH)2D3, mediate the developmental regulation of OC gene transcription. In this study, we established that the -1097 to +23 promoter ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00093a022
更新日期:1993-10-26 00:00:00
abstract::ISU-type proteins mediate cluster transfer to apo protein targets. Rate constants have been determined for cluster transfer from ISU to apo Fd for both Homo sapiens and Schizosaccharomyces pombe proteins, and cross reactions have also been examined. Substitution of a key aspartate residue of ISU is found to decrease t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0256781
更新日期:2002-07-16 00:00:00
abstract::Reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) is a key objective in the treatment of OP poisoning. This study with native, wild-type, and mutant recombinant DNA-expressed AChEs, each inhibited by representative OP compounds, establishes a relationship between edrophonium acceleration of ox...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9905720
更新日期:1999-08-03 00:00:00
abstract::Kinetic studies of reactions between fluorescein and antifluorescein antibody produced during early, intermediate, and late stages of the immune response have been carried out utilizing both fluorescence intensity and polarization measurements in the static (time constant similar to 5 sec) and in the stopped-flow mode...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00688a009
更新日期:1975-08-26 00:00:00
abstract::The heterotrimeric G protein subunit, alpha(s), can move reversibly from plasma membranes to cytoplasm in response to activation by GPCRs or activating mutations. We examined the importance of the unique N-terminus of alpha(s) in this translocation in cultured cells. alpha(s) contains a single site for palmitoylation ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi025533u
更新日期:2002-07-30 00:00:00
abstract::Osmoregulatory transporters stimulate bacterial growth by mediating osmoprotectant uptake in response to increasing osmotic pressure. The ProP protein of Escherichia coli transports proline and other osmoprotectants. Like LacY, ProP is a member of the major facilitator superfamily and a H(+)-solute symporter. ProP is ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101281f
更新日期:2010-10-19 00:00:00
abstract::Oligoribonucleotide binding to baker's yeast initiator tRNA was measured by equilibrium dialysis in order to determine which regions of the tRNA were free to bind complementary oligomers and which were involved in secondary and tertiary structure. Association constants of trinucleoside diphosphates and tetranucleoside...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00686a004
更新日期:1975-07-29 00:00:00
abstract::Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone involved in the maintenance of the corpus luteum in early pregnancy. The free alpha-subunit of hCG has a biological activity of its own, namely, stimulation of prolactin secretion from term pregnancy decidual cells [Blithe, D. L., et al. (1991)...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9718548
更新日期:1998-02-17 00:00:00