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PEG Moiety (peg + moiety)
Selected AbstractsDesign, synthesis, characterization and in-vivo activity of a novel salmon calcitonin conjugate containing a novel PEG-lipid moietyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2010Weiqiang Cheng Abstract Objectives The aim of the study was to explore (1) the synthesis of a novel poly(ethylene glycol) modified lipid (PEG-lipid, PL) containing a chemically active tri-block linker, ,-maleimido lysine (Mal), and its conjugation with salmon calcitonin (sCT), and (2) the biophysical properties and activity of the resulting conjugate, Mal-PL-sCT, relative to the control, 2PEG-Mal-sCT, which comprises sCT conjugated with ,-palmitoyl- N -,-maleimido- l -lysine at cysteine 1 and cysteine 7, and PEG moieties at lysine 11 and lysine 18 via a conventional stepwise method. Methods The PEG-lipid was obtained by condensing palmitic acid derivative of ,-maleimido lysine with methoxy poly(ethylene glycol) amine. Under reductive conditions, the PEG-lipid readily reacted with sCT to yield the resultant compound, Mal-PL-sCT. Key findings Dynamic light scattering analyses suggested that Mal-PL-sCT and 2PEG-Mal-sCT exhibited robust helical structures with a high tendency to aggregate in water. Both compounds were more stable against intestinal degradation than sCT, although Mal-PL-sCT was less stable than 2PEG-Mal-sCT. However, 2PEG-Mal-sCT did not possess hypocalcaemic activity while Mal-PL-sCT retained the hypocalcaemic activity of sCT when it was subcutaneously injected in the rat model. Multiple functional groups may be conjugated to a peptide via a tri-block linker without the risk of obliterating the intrinsic bioactivity of the peptide. Conclusions The resultant novel PEG-lipid has a potential role to optimize protein and peptide delivery. [source] Single-Molecule Behavior of Dendritic Poly(ethylene glycol) Structures towards Lithium IonsCHEMISTRY - A EUROPEAN JOURNAL, Issue 40 2009Daihua Tang Dr. PEG-ged out! Dendritic poly(ethylene glycol) (PEG) D exhibits excellent single-molecule behavior to lithium ions, and has been characterized by MALDI-TOF-MS and TOF-ESI-MS. Since commercially available linear PEG structures are not monocomponent, constructing dendritic structures may become a good strategy to achieve higher molecular-weight PEG moieties. [source] pH dependent self assembly of ,-amyloid(10-35) and ,-amyloid(10-35)-PEG3000JOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3-1 2000P. Thiyagarajan Small angle neutron and x-ray scattering (SANS/SAXS) studies were conducted on the structure of the aggregates formed from both the truncated model peptide ,-Amyloid(10-35) (A,10-35) and a block copolymer ,-Amyloid(10-35)-PEG3000 (A,10-35 -PEG) in D2O at pHs from 3.0 to 7.0. These studies indicate that A,10-35 aggregates into rod-like particles (fibril) and their radii are strongly dependent on the pH of the solution. The fibril-fibril association in A,10-35 solutions is less at pH < 5.6, but becomes larger at higher pH. A,10-35 -PEG also assembles into rod-like particles whose radius is larger by about 30 Å than that for A,10-35 fibril at pH 4.2, while it is about 23 Å larger at higher pH. Contrast matching SAXS/SANS experiments that eliminate the coherent scattering from PEG reveal that PEG moiety is located at the periphery of the fibril. Also the mass per unit length of the peptide portion is similar for both A,10-35 and A,10-35 fibrils at pH 5.6. The mass per unit length of the rods from SANS provides key information on the packing of A,10-35 peptides in the fibril. [source] Modulation of protein aggregation by polyethylene glycol conjugation: GCSF as a case studyPROTEIN SCIENCE, Issue 5 2006Rahul S. Rajan Abstract Polyethylene glycol (PEG) conjugation to proteins has emerged as an important technology to produce drug molecules with sustained duration in the body. However, the implications of PEG conjugation to protein aggregation have not been well understood. In this study, conducted under physiological pH and temperature, N-terminal attachment of a 20 kDa PEG moiety to GCSF had the ability to (1) prevent protein precipitation by rendering the aggregates soluble, and (2) slow the rate of aggregation relative to GCSF. Our data suggest that PEG-GCSF solubility was mediated by favorable solvation of water molecules around the PEG group. PEG-GCSF appeared to aggregate on the same pathway as that of GCSF, as evidenced by (a) almost identical secondary structural transitions accompanying aggregation, (b) almost identical covalent character in the aggregates, and (c) the ability of PEG-GCSF to rescue GCSF precipitation. To understand the role of PEG length, the aggregation properties of free GCSF were compared to 5kPEG-GCSF and 20kPEG-GCSF. It was observed that even 5kPEG-GCSF avoided precipitation by forming soluble aggregates, and the stability toward aggregation was vastly improved compared to GCSF, but only marginally less stable than the 20kPEG-GCSF. Biological activity measurements demonstrated that both 5kPEG-GCSF and 20kPEG-GCSF retained greater activity after incubation at physiological conditions than free GCSF, consistent with the stability measurements. The data is most compatible with a model where PEG conjugation preserves the mechanism underlying protein aggregation in GCSF, steric hindrance by PEG influences aggregation rate, while aqueous solubility is mediated by polar PEG groups on the aggregate surface. [source] Improvement of retroviral vectors by coating with poly(ethylene glycol)-poly(L -lysine) block copolymer (PEG-PLL)THE JOURNAL OF GENE MEDICINE, Issue 4 2004Hiromichi Katakura Abstract Background Although some cationic reagents, such as polybrene, improve gene transduction in vitro, their use in vivo is prohibited due to their toxicity to the exposed cells. This paper demonstrates that a new cationic reagent, poly(ethylene glycol)-poly(L -lysine) block copolymer (PEG-PLL), improves gene transduction with retroviral vectors without increasing cell toxicity. Methods A retroviral vector derived from the Moloney leukemia virus, containing the lacZ gene, was modified with PEG-PLL prior to transduction into NIH3T3, Lewis lung carcinoma, and primary cultured mouse brain cells. LacZ transduction efficacy was evaluated by counting the number of X-Gal-positive cells. Results We have demonstrated that PEG-PLL is able to stably modify the viral particle surface due to the affinity of the PEG moiety to the biomembrane, and neutralizes negative charges by the cationic nature of the poly-lysine residue. Thus, PEG-PLL increased the gene transduction efficiency and minimized cell toxicity because free PEG-PLL was removable by centrifugation. We have shown that PEG-PLL increased the viral gene transduction efficiency 3- to 7-fold with NIH3T3 or Lewis lung carcinoma cell lines without increasing cytotoxicity. It improved retroviral gene transduction efficacy even against labile cells, such as primary cultured brain cells. Conclusions PEG-PLL is a novel reagent that improves retroviral gene transduction efficacy without increasing cytotoxicity. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||