Coupling of Monomethoxypolyethyleneglycols to Proteins via Active Esters

Boccù, E; Largajolli, Roberta; Veronese, Francesco M.

doi:10.1515/znc-1983-1-218

Cited by 43 publications

(20 citation statements)

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“…4A, Table 2). This phenomenon was exactly reproduced in our in vitro of PEG (7,24). Thus, mPEG can create antigenically silent (stealth) cells and imperceptible change of islet size model system simulating in vivo presensitized condition.…”

Section: The Effect Of Pegylation On Transplanted Isletssupporting

confidence: 82%

Cell Surface Modification by Activated Polyethylene Glycol Prevents Allosensitization after Islet Transplantation

et al. 2008

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The necessity to transplant islet tissue without the need for immunosuppressant therapy has led to the development of materials for immune modulation. Pegylation makes islets antigenically silent, protecting them from the adsorption of foreign protein and thus avoiding immune injury. The aim of this study is to determine whether pegylation of islets prolongs islet survival and function both during tissue culture and posttransplantation. We used cyanuric chloride-activated methoxy-polyethylene glycol for cell surface modification. To detect the pegylation effect on splenocytes, we measured antibody binding inhibition and abrogation of lymphocyte proliferation. To detect the pegylation effect on islet grafts, we performed rodent islet transplantation. Islet viability and function were maintained after pegylation. Pegylated islets showed a 90% decrease in antibody binding and decreased lymphocyte proliferation in a mixed lymphocyte culture. However, when pegylated islets were transplanted, no prolongation of graft survival was observed. When a subtherapeutic dose of immunosuppressant was given at the time of transplantation of pegylated islets, islet graft survival was significantly prolonged. In addition, when rats were sensitized with donor splenocytes, graft survival was prolonged by pegylation. We observed that pegylation of islets, combined with a subtherapeutic dose of immunosuppressant, protects the graft from rejection. Prolonged graft survival in sensitized recipients showed that pegylation of islets shifted the pattern of rejection from an acute humoral response to a less aggressive cellular alloresponse.

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Section: The Effect Of Pegylation On Transplanted Isletssupporting

confidence: 82%

Cell Surface Modification by Activated Polyethylene Glycol Prevents Allosensitization after Islet Transplantation

et al. 2008

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“…Low degrees of oxidation were obtained using activated manganese dioxide, 29 2,2,6,6-tetramethylpiperidin-1-yloxyl (TEMPO)-CuCl 2 -CaH 2 , 30 pyridinium chlorochromate, and the Corey-Kim procedure. Complete oxidation of all the PEG hydroxy groups was not ideal for the synthesis of a polymer with comparable hydroxy and amine functionalities.…”

Section: (A) Oxidation Of Pegmentioning

confidence: 99%

HYDRA: A novel hydroxy and amine functionalised resin synthesised by reductive amination of PEG aldehyde and a polyamine

Groth

Grötli

Lubell

et al. 2000

J. Chem. Soc., Perkin Trans. 1

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A chemically inert poly(ethylene glycol) (PEG)-based resin was synthesised by reductive amination of a mixture of mono-and dialdehyde PEG 1500 and the branched cross-linker tris(2-aminoethyl)amine. This unique concept of resin polymerisation yields a polar resin with two functionalities present (OH and NH). The resin loading could be tuned between 0.33 and 0.80 mmol OH per gram and 0.88 and 0.24 mmol NH per gram by varying the monomer composition in the polymerisation mixture. The resin was found to exhibit excellent swelling properties in a broad range of solvents, and was stable towards strongly acidic and basic conditions for weeks. Furthermore, both an octaand a decapeptide were successfully assembled independently on the different functionalities. In addition, the resin was shown to be fully permeable to a 27 kDa protease.

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“…46 ,48 However, preparation of 3c, starting from hydroxyl terminated mPEG, involves 4 to 5 synthetic steps. 48 Formation of urethane (carbamate) linkages between the amino groups of a protein and PEG overcomes the problem of hydrolytic release of the polymer chains.…”

Section: Most Commonly Used Peg-based Reagentsmentioning

confidence: 99%

Use of Functionalized Poly(Ethylene Glycol)s for Modification of Polypeptides

Zalipsky

Lee

1992

Poly(Ethylene Glycol) Chemistry

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The unique properties of poly(ethylene glycol) (or PEG) and its general compatibility with polypeptide materials facilitated development of a variety of different applications of this polymer. 1 -ll A marked proportion of these applications involve the use of covalently linked polypeptide-PEG adducts (reviewed else-where5-11 ). For example, a number of PEG-enzymes were shown to be useful as catalysts, soluble and active in organic solvents. 7 Due to the affinity to the upper phase of PEG/Dextran and PEG/salt two-phase systems, PEG-modified proteins were proven useful both as diagnostic tools 8 and in preparative separations of biological cells. 9 Unquestionably, the properties of polymer-polypeptide conjugates in vivo were a significant reason for the substantial amount of research reported in the area during the last two decades. It has been repeatedly demonstrated that covalent attachment of multiple strands of PEG to proteins produces conjugates with dramatically reduced immunogenicity and antigenicity. IO Such preparations also show great resistance to proteolytic digestion, and remain present in the bloodstream a considerably longer time than the parent polypeptides. These beneficial properties of modified polypeptides allowed development of a number of PEG-modified therapeutic proteins. IO Slight to moderate modification of potent allergenic proteins with PEG can often be SAMUEL ZALIPSKY and CHYI LEE· Enzon, Inc., South Plainfield, New Jersey 07080. Present address for s. Z.:

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Coupling of Monomethoxypolyethyleneglycols to Proteins via Active Esters

Cited by 43 publications

References 0 publications

Cell Surface Modification by Activated Polyethylene Glycol Prevents Allosensitization after Islet Transplantation

Cell Surface Modification by Activated Polyethylene Glycol Prevents Allosensitization after Islet Transplantation

HYDRA: A novel hydroxy and amine functionalised resin synthesised by reductive amination of PEG aldehyde and a polyamine

Use of Functionalized Poly(Ethylene Glycol)s for Modification of Polypeptides

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