Degradable linkers

In addition, the degradation properties of hydrogels were adjusted by incorporation of degradable linkers. By using enzyme-sensitive peptide sequences, cell-responsive biomaterials that mimic the proteolytic recognition of natural ECMs... 

The modification reaction is well controlled and the number of linkers introduced per protein molecule can be tailored by changing the reaction conditions. LZM can be modified with up to three methacrylamide moieties without major conformational changes. The lytic activity was still 60% after introducing an average of 2.3 methacrylamide units. The modified LZM was successfully immobilized into a hydrogel network and subsequently released by reduction of the degradable linker. 

Poly(acrylic acid) and Poly(methacrylic acid). Poly(acryHc acid) (8) (PAA) may be prepared by polymerization of the monomer with conventional free-radical initiators using the monomer either undiluted (36) (with cross-linker for superadsorber appHcations) or in aqueous solution. Photochemical polymerization (sensitized by benzoin) of methyl acrylate in ethanol solution at —78° C provides a syndiotactic form (37) that can be hydrolyzed to syndiotactic PAA. From academic studies, alkaline hydrolysis of the methyl ester requires a lower time than acid hydrolysis of the polymeric ester, and can lead to oxidative degradation of the polymer (38). Po1y(meth acrylic acid) (PMAA) (9) is prepared only by the direct polymerization of the acid monomer it is not readily obtained by the hydrolysis of methyl methacrylate. 

The use of y-ray induced radical pol5unerization proved to be a successful alternative for the radical co-polymer-ization of metal complexes with ligands containing acrylic C—C double bonds [100-102,129,130]. In particular, the palladium(II) complex cw-[PdCl2(ICPA)2] (1, Scheme 4) was co-polymerized in DMF solution with DMA and MBAA (cross-linker, 4% mol), with no degradation of the metal center [100,101]. 

Degradation of the ligand or the linker to the support must be avoided, as this results in metal leaching and catalyst deactivation. For example, phosphorus ligands are sensitive to oxidizing impurities in the feed (peroxides). 

A key aspect of any synthesis strategy on a polymeric support is the linkage element, which acts as a tether to the polymeric support. Ideally, the linker should be stable to all reaction conditions used in a synthesis sequence and should be cleaved quantitatively under conditions that do not degrade the desired target molecule [6]. In this overview the different kinds of linkers and the synthetic transformations that can be used on polymeric supports will be presented. At the end, synthetic strategies for the synthesis of heterocycles and natural products will be mentioned. 

Many acid-labile linkers are used to assemble combinatorial libraries. Compounds are cleaved in the final step by TFA/DCM solution with various concentrations for a certain period of time. Mild cleavage conditions may lead to incomplete cleavage of the desired compound from a solid support. On the other hand harsh conditions may cause compound degradation and side reactions. Harsh conditions will also cause the partial breakdown of resin and the leaching of unidentified impurities into the final products. Harsh cleavage conditions demand the stabihty of all compounds under such conditions. This may limit the scope of combinatorial synthesis... 

Epoxy-alkanol >240h 240h Slow degradation of cross-linker 28,31... 

QDs have been shown to be quite stable to metabohc degradation (with the exception of problems associated with heavy metal leachants) [ 177,180]. QDs can be conjugated to the linker [181] (e.g., avidin, protein A or protein G, or a secondary antibody) by covalent binding, passive adsorption, multivalent chelation or by electrostatic interactions [182,183]. 

Multiplex PCR amplification can apparently tolerate degraded DNA because the size of PCR products generated for subsequent hybridization is 100 50 base pairs. However, the 10 K mapping array and the 100 K and 500 K arrays use a specific restriction enzyme to digest the genomic DNA for subsequent ligation with a specific DNA linker. The DNA linkers then act as binding sites for the specific primer to initiate PCR amplification... 

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