Abstract:
:The importance of therapeutic recombinant proteins in medicine has led to a variety of tactics to increase their circulation time or to enable routes of administration other than injection. One clinically successful tactic to improve both protein circulation and delivery is to fuse the Fc domain of IgG to therapeutic proteins so that the resulting fusion proteins interact with the human neonatal Fc receptor (FcRn). As an alternative to grafting the high molecular weight Fc domain to therapeutic proteins, we have modified their N and/or C termini with a short peptide sequence that interacts with FcRn. Our strategy was motivated by results [Mezo AR, et al. (2008) Proc Natl Acad Sci USA 105:2337-2342] that identified peptides that compete with human IgG for FcRn. The small size and simple structure of the FcRn-binding peptide (FcBP) allows for expression of FcBP fusion proteins in Escherichia coli and results in their pH-dependent binding to FcRn with an affinity comparable to that of IgG. The FcBP fusion proteins are internalized, recycled, and transcytosed across cell monolayers that express FcRn. This strategy has the potential to improve protein transport across epithelial barriers, which could lead to noninvasive administration and also enable longer half-lives of therapeutic proteins.
journal_name
Proc Natl Acad Sci U S Aauthors
Sockolosky JT,Tiffany MR,Szoka FCdoi
10.1073/pnas.1208857109subject
Has Abstractpub_date
2012-10-02 00:00:00pages
16095-100issue
40eissn
0027-8424issn
1091-6490pii
1208857109journal_volume
109pub_type
杂志文章abstract::DNA "breathing" is a thermally driven process in which base-paired DNA sequences transiently adopt local conformations that depart from their most stable structures. Polymerases and other proteins of genome expression require access to single-stranded DNA coding templates located in the double-stranded DNA "interior,"...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1314862110
更新日期:2013-10-22 00:00:00
abstract::An increase in free Ca2+ triggers exocytosis in pituitary nerve terminals leading to an increase in membrane area and membrane capacitance. When Ca2+ is increased by step depolarization, an instantaneous capacitance increase during the first 80 ms is followed by a slow increase extending over several seconds. We measu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.12.5267
更新日期:1994-06-07 00:00:00
abstract::To visualize histone acetylation in living cells, we developed a genetically encoded fluorescent resonance energy transfer (FRET)-based indicator. Response of the indicator reflects changes in the acetylation state of both K5 and K8 in histone H4. Using this acetylation indicator, we were able to monitor the dynamic f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0902150106
更新日期:2009-09-22 00:00:00
abstract::The immunity protein to colicin A (Cai), which is constitutively expressed at a very low level in Escherichia coli strains, has been studied in recombinant plasmid constructs allowing expression of various immunity fusion proteins under the control of inducible promoters. The 13-amino acid NH2-terminal region of Cai w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.3.689
更新日期:1988-02-01 00:00:00
abstract::Transient cytosolic Ca(2+) ([Ca(2+)](cyt)) elevations are early events in plant signaling pathways including those related to abiotic stress. The restoration of [Ca(2+)](cyt) to prestimulus levels involves ATP-driven Ca(2+) pumps, but direct evidence for an essential role of a plant Ca(2+)-ATPase in abiotic stress ada...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0800864105
更新日期:2008-12-09 00:00:00
abstract::In the basal ganglia, inputs from the nucleus accumbens (NAc) are transmitted through both direct and indirect pathways and control reward-based learning. In the NAc, dopamine (DA) serves as a key neurotransmitter, modulating these two parallel pathways. This study explored how reward learning and its flexibility are ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1210797109
更新日期:2012-07-31 00:00:00
abstract::There are certain genes on the sex chromosome of Drosophila for which the female contains twice as many copies as the male. Some of the genes in this group produce the same phenotype in each sex despite the dosage difference and are said, therefore, to manifest dosage compensation. The structural genes for glucose-6-p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.62.2.528
更新日期:1969-02-01 00:00:00
abstract::Schiff bases of the diamines 1,3-diaminopropane, putrescine, and cadaverine and the polyamines spermidine and spermine with pyridoxal or pyridoxal phosphate occur in human urine, as shown by gas chromatographic/mass spectrometric selected ion-monitoring techniques. By use of synthetic standards, procedures were devise...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.12.6652
更新日期:1979-12-01 00:00:00
abstract::Autoantibodies directed against the cell surface receptors for insulin are found in some patients with extreme insulin resistance. These antibodies specifically inhibit the binding of insulin to its receptor. A purified IgG fraction from one patient's plasma was labeled with 125I. The 125I-labeled antireceptor antibod...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.11.4115
更新日期:1976-11-01 00:00:00
abstract::Inwardly rectifying potassium (K(+)) channels gated by G proteins (Kir3.x family) are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by G(betagamma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.080572297
更新日期:2000-05-09 00:00:00
abstract::Intrinsically disordered proteins (IDPs) are characterized by a lack of defined structure. Instead, they populate ensembles of rapidly interconverting conformations with marginal structural stabilities. Changes in solution conditions such as temperature and crowding agents consequently affect IDPs more than their fold...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1705105114
更新日期:2017-09-12 00:00:00
abstract::In t(15;17) acute promyelocytic leukemia, all-trans retinoic acid (RA) induces leukemic cell maturation in vitro and remission in acute promyelocytic leukemia patients, but in vivo treatments invariably lead to relapse with resistance to RA. NB4, a maturation-inducible cell line, and NB4-RAr sublines (R1 and R2) displ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.18.8428
更新日期:1994-08-30 00:00:00
abstract::We previously demonstrated that the primary region of factor IX and IXa responsible for saturable specific binding to bovine aortic endothelial cells resides in residues 3-11 at the amino terminus of factor IX. We also demonstrated that mutations of lysine to alanine at residue 5, factor IX K5A, or valine to lysine at...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.20.11068
更新日期:1996-10-01 00:00:00
abstract::To study the structure and function of the gene for parathyroid hormone, we obtained recombinant plasmids containing bovine parathyroid hormone cDNA. The nucleotide sequence at the 5' terminus (relative to the sense strand) of the cDNA insert in a recombinant plasmid, pPTHi4, was different from that previously reporte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.7.4073
更新日期:1981-07-01 00:00:00
abstract::Paracoccidioidomycosis, a disease caused by Paracoccidioides brasiliensis, which is endemic to Latin America, is much more common in men than women, suggesting a role for hormonal factors. We recently showed that two other yeasts possess steroid binding proteins and postulated that these receptor-like molecules repres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.24.7659
更新日期:1983-12-01 00:00:00
abstract::Human interleukin 12 and interleukin 23 (IL12/23) influence susceptibility or resistance to multiple diseases. However, the reasons underlying individual differences in IL12/23 sensitivity remain poorly understood. Here we report that in human peripheral blood mononuclear cells (PBMCs) and inflamed lungs, the majority...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1515978112
更新日期:2015-12-15 00:00:00
abstract::Junctions that mediate excitation-contraction (e-c) coupling are formed between the sarcoplasmic reticulum (SR) and either the surface membrane or the transverse (T) tubules in normal skeletal muscle. Two structural components of the junctions, the feet of the SR and the tetrads of T tubules, have been identified resp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.8.3381
更新日期:1995-04-11 00:00:00
abstract::Langerhans cells are a subset of dendritic cells (DCs) found in the human epidermis with unique morphological and molecular properties that enable their function as "sentinels" of the immune system. DCs are pivotal in the initiation and regulation of primary MHC class I restricted T lymphocyte immune responses and are...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.071477498
更新日期:2001-03-27 00:00:00
abstract::During protein synthesis, elongation factor G (EF-G) binds to the ribosome and promotes the step of translocation, a process in which tRNA moves from the A to the P site of the ribosome and the mRNA is advanced by one codon. By using three-dimensional cryo-electron microscopy, we have visualized EF-G in a ribosome-EF-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.11.6134
更新日期:1998-05-26 00:00:00
abstract::The cellulose synthesizing terminal complex consisting of subunits A, B, C, and D in Acetobacter xylinum spans the outer and inner cell membranes to synthesize and extrude glucan chains, which are assembled into subelementary fibrils and further into a ribbon. We determined the structures of subunit D (AxCeSD/AxBcsD) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1000601107
更新日期:2010-10-19 00:00:00
abstract::The reactions catalyzed by Mo enzymes each find the product differing from the substrate by two electrons and two protons (or some multiple thereof). The coordination chemistry of Mo suggests that there is a distinct relationship between acid-base and redox properties of Mo complexes, and that a coupled electron-proto...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.4.988
更新日期:1973-04-01 00:00:00
abstract::Anaerobic beta-galactoside transport in whole cells and membrane vesicles from E. coli ML 308-225 is coupled to the oxidation of alpha-glycerol-P or D-lactate with fumarate as an electron acceptor. Alternatively, anaerobic beta-galactoside transport may be coupled to the oxidation of formate utilizing nitrate as elect...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.12.3376
更新日期:1973-12-01 00:00:00
abstract::The kinetics of hepatic uptake and degradation of sphingomyelin/cholesterol (2:1, M/M) small unilamellar liposomes were investigated in a BALB/c mouse. The tissue distribution of liposomes was determined by scintillation spectrometry. The percentage of intact liposomes in tissues was estimated by the technique of gamm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.7.4030
更新日期:1980-07-01 00:00:00
abstract::One way to dissect the antibody response to an invading microorganism is to clone the antibody repertoire from immune donors and subsequently characterize the specific antibodies. Recently, methodological advances have allowed investigations of neutralizing antibodies against hepatitis C virus (HCV) in vitro. We have ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705522104
更新日期:2007-10-09 00:00:00
abstract::The overall structure of the transition-state and intermediate ensembles observed experimentally for dihydrofolate reductase and interleukin-1beta can be obtained by using simplified models that have almost no energetic frustration. The predictive power of these models suggests that, even for these very large proteins...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.100547897
更新日期:2000-05-23 00:00:00
abstract::The pH gradient (delta pH) across the membrane of bovine neurohypophysial granules was estimated by using the [14C]methylamine partition technique. The granule membrane showed high permeability to sugars such as sucrose or sorbitol and to cations. Granules suspended in sucrose medium showed an acidic internal delta pH...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.2.476
更新日期:1982-01-01 00:00:00
abstract::We show that a drop of liquid a few hundred microns in diameter placed under a solid, elastic, thin film (∼10 μm thick) causes it to bulge by tens of microns. The deformed shape is governed by equilibrium of tensions exerted by the various interfaces and the solid film, a form of Neumann's triangle. Unlike Young's equ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1304587110
更新日期:2013-06-25 00:00:00
abstract::To scrutinize how a protein folds at atomic resolution, we performed 200 molecular dynamics simulations (each of 50 ns) of the miniprotein Trp-cage on the computational grid. Within the trajectories, 58 folding and 31 unfolding events were identified and subjected to extensive comparison and classification. Based on a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407015102
更新日期:2004-12-21 00:00:00
abstract::MXenes, a new family of 2D materials, combine hydrophilic surfaces with metallic conductivity. Delamination of MXene produces single-layer nanosheets with thickness of about a nanometer and lateral size of the order of micrometers. The high aspect ratio of delaminated MXene renders it promising nanofiller in multifunc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1414215111
更新日期:2014-11-25 00:00:00
abstract::Bioluminescence-based imaging of living cells has become an important tool in biological and medical research. However, many bioluminescence imaging applications are limited by the requirement of an externally provided luciferin substrate and the low bioluminescence signal which restricts the sensitivity and spatiotem...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1913616116
更新日期:2019-12-02 00:00:00