Polyethylene glycol linkers

Carbohydration and polyethylene glycol linkers were combined with chemoselective conjugation to optimize the pharmacokinetics of the peptides investigated. Oxime formation was successfully adopted for chemoselective F-labeling of an aminooxy-modified affibody (Namavari et al. 2008) and a suitable derivative of the hormone leptin (Flavell et al. 2008). Recently, the [ F]FBA synthesis was automated and yielded [ F]FBA after 45 min in radiochemical yields of 54% and radiochemical purity of >99% after automated cartridge purification (Speranza et al. 2009). 

A soluble aminomethylated polyethylene glycol and a succinoyl linker were used to support a 9-fluorenylmethyl group for solution-phase glycosylation by the sulfoxide method. With the help of temporary protection by a 6-O-triphenylmethyl ether, the method could be carried out iteratively to form disaccharides (Scheme 4.69) [379],... 

It has long been recognized that polymeric supports for oligosaccharide synthesis do not need to be insoluble.33 Wang et al. applied the sulfoxide glycosylation method to the synthesis of disaccharide 79 (Scheme 3.14). The key feature of this work was the base-labile linker. Sulfoxide 74 was used to glycosylate polyethylene glycol... 

An alternative coupling strategy that avoids potential steric hindrance of drug action and eliminates the need for cleavability utilizes long, flexible spacer arms, e.g. biotin-derivatized polyethylene glycol (PEG) linkers with molecular weights of 2000 or 5000 Da [93,94]. 

The solution phase synthesis of peptides often results in mixtures of labelled, unlabelled compounds along with other impurities and requires extensive purification. A route using a solid phase approach [polyethylene glycol-poly-styrene PEG-PS derivatised with a xanthen-2-oxovalerate (XAL) linker] was recently developed [193] (Scheme 44). 

EDC FDPP Fmoc HOBt LiHMDS MAMP MCPBA MeOPEG NCA NMP PAL PASP PBP PEG SASRIN TEA TFA TMAD N-Ethyl-N - [ 3 - (dimethy lamino)propy 1] -c arbodiimide hydrochloride Pentafluoro phenyldiphenyl phosphate 9 -Fluoreny lme thoxy c arbony 1 Hydroxybenzotriazol Lithium hexamethyldisilazane Merrifield, alpha methoxy phenyl resin w-Chloroperbenzoic acid Methoxy polyethylene glycol /V-Carboxv a-aminoacid anhydride /V - M e t h v 1 pyrrol i do n e Peptide amide linker Polymer assisted solution phase Penicillin-binding proteins Polyethylene glycol Super acid sensitive resin Triethylamine Trifluoroacetic acid Tetramethylamine azodicarboxylate. 

Bradley described the first solid-phase synthesis of PAMAM dendrimers in 1997 [220]. To this end, phthaloyl-protected norspermidine was coupled to aminomethyl functionalised polystyrene-polyethylene-glycol resin ((PS-PEG)-NH2) through an acid-labile linker (see Fig. 23). PAMAM dendrons were assembled by treating deprotected scaffold-bound resin 24 first with an excess of methyl acrylate... 

Several complexities must be addressed in order to fully understand the mode(s) of binding and the effects of the linker and dye on the stability of the duplex. The fact that the greatest stability was observed with an alkyl chain linker may be somewhat problematic in a dirty sample, as might be encountered in the analysis of crudely prepared real-world samples. In such cases, the alkyl chain could provide sites at which proteins and lipids might adsorb. Quantum yields are sufficient such that polyethylene glycol tethers could be used in real-world sensor configurations. 

Fig. 2. Application of the polyethylene glycol-co-monomethyl ether (MPEG) solid support with an a,a -dioxyxylyl (DOX) diether linker for oligosaccharide synthesis in solution.

Tethered SWCNTs and interconnections between individual SWCNTs using a,to-dinitrenes as the molecular linker (Scheme 1.20) were reported the first time in 2003 by Holzinger et al. [157]. The bisnitrenes were derived from thermolysis of polyethylene glycol) PEG 600 bisazidocarbonate the covalent linkage was characterized by SEM studies, XPS, X-ray diffractograms and Raman spectra [157]. 

Different polyethylene glycol polymers were used in various papers and proved to be very reliable and useful for different classes of molecules their use for the synthesis of peptides [180, 181], of peptidomimetics [182] and of oligosaccharide libraries [183] was reported as the development and the use of a new PEG-linked traceless linker [184, 185], the selection of ligands for asymmetric Sharpless dihydroxylation [186-188], the use of PEG-linked triarylphosphines for LPCS requiring Mitsunobu or Staudinger conditions [189], the use of PEG-based supports to prepare a library of [l,4]oxazepine-7-ones [190] and the use of PEG-supported Schiff bases for the synthesis of a-substituted amino acids [191], Other examples of soluble polymers used for LPCS may include cellulose[192], polyacrylamide [193] polyvinyl alcohol [194, 195], various copolymers [196, 197] and NCPS [198-200]. Three excellent reviews [201-203] summarized the properties of PEG and other soluble polymers and their applications to the synthesis of peptides, oligonucleotides,... 

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