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71.
Polymer conjugation increases an enzyme's circulation time and stability for use as a therapeutic agent, but this attachment indubitably affects its properties. Covalent attachment of multiple polyethylene glycol chains with sizes of either 2, 5, 10, or 20 kDa increases the molecular weight and hydrodynamic radius of the model enzyme trypsin. The sizes of these polymer-enzyme conjugates are increased to be within the recommended limits for PDEPT applications. The T(d) increases from 49 to 60 °C to expand the enzyme's workable range of conditions. This functionalization with PEG polymers of varying lengths maintains trypsin's enzymatic activity. Conjugate activities are 79-120% that of native trypsin at room temperature and 221-432% that of trypsin at 37 °C. 相似文献
72.
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Standley SM Mende I Goh SL Kwon YJ Beaudette TT Engleman EG Fréchet JM 《Bioconjugate chemistry》2007,18(1):77-83
The development of multicomponent biotherapeutic carriers is an important challenge in the field of drug delivery, particularly in the area of protein-based vaccines. While the delivery of protein antigens to antigen presenting cells (APCs) is crucial for this type of vaccination, the incorporation of additional adjuvants may be just as important in order to generate more potent immune responses. This article presents the synthesis and biological evaluation of carrier particles that both deliver a protein payload to APCs and display receptor ligands for the enhancement of APC immunostimulation. Particles displaying CpG oligonucleotide ligands for Toll-like receptor 9 were synthesized. The addition of CpG DNA to the particles led to a 45-fold increase in the secretion of interleukin-12, a cytokine that aids in T-cell activation, and a significant increase in the expression of costimulatory molecules by APCs. Moreover, vaccination with particles containing both ovalbumin (OVA) and CpG DNA induced a superior OVA-specific CD8 T-cell response in vivo, as measured by increased OVA-specific CD8 T-cell proliferation, secretion of the proinflammatory cytokine IFN-gamma, and the induction of OVA-specific cytotoxicity. 相似文献
74.
75.
We have recently reported biodegradable cationic micelles self-assembled from an amphiphilic copolymer, poly{(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl)methyl bis(ethylene)ammonium bromide]sebacate} (P(MDS-co-CES)), which were utilized to deliver a drug and nucleic acid simultaneously, and a synergistic effect was achieved. In this paper, synthesis and characterization of the polymer is presented in details, focusing on micelle formation and DNA binding under various conditions, cytotoxicity, in-vitro degradation, and gene transfection in various cell lines. The polymer was degradable and formed micelles at very low concentrations even in an environment with high salt concentration. These micelles fabricated at pH 4.6 had an average size of less than 82 nm and zeta potential of up to 84 +/- 5 mV, displaying strong DNA binding ability. They induced high gene expression efficiency in various cell lines, which was significantly greater than poly(ethylenimine) (PEI) especially in 4T1 mouse and MDA-MB-231 human breast cancer cell lines, but they were less cytotoxic. These cationic micelles may provide a promising nonviral vector for gene delivery. 相似文献
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79.
Olivier Monteuuis Doreen K. S. Goh Charles Garcia David Alloysius Jikos Gidiman Roberto Bacilieri Gilles Chaix 《Tree Genetics & Genomes》2011,7(6):1263-1275
Forty-two different genetic origins of teak (Tectona grandis) comprising 26 open-pollinated families from a clonal seed orchard (CSO) were planted in a replicated trial under 2,500 mm
of annual rainfall and no distinct dry season, in 1997, in Sabah, East Malaysia. The trees were measured or scored for various
traits at 13, 35, 49, 61, 72, 85, 96, and 106 months after planting. Mortality rate, height (H), diameter at breast height
(DBH), volume (V), and fork height (FH) varied strongly among populations and origins. The best population means after 106 months for growth
H (21.1 m), DBH (21.1 cm), and V (278 dm3) were for the CSO families. Narrow sense heritabilities for the CSO families increased gradually with age but remained lower
after 106 months for DBH (h
2 = 0.24) and V (h
2 = 0.34) than for H (h
2 = 0.51) and FH (h
2 = 0.56). Overall, the CSO families were also straighter, less forked, and grew more vertically than the native provenance
and seed-derived sources. Such differences did not exist for flowering ability, and at 106 months, the great majority of the
trees of the various origins had not yet entered the flowering stage. Overall, at 106 months, the phenotypic correlations
between the various quantitative and qualitative traits were weak, except between straightness and bending with values higher
than 0.50. These findings confirm the usefulness of CSO for teak improvement and demonstrate the beneficial influence of wet
tropical conditions on traits of major economical importance for this species. 相似文献
80.
Patel NS Nandra KK Brines M Collino M Wong WF Kapoor A Benetti E Goh FY Fantozzi R Cerami A Thiemermann C 《Molecular medicine (Cambridge, Mass.)》2011,17(9-10):883-892
Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect-an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB. 相似文献