Succinyl linkage

The succinyl linkage, 39 (Fig. 7), that was introduced in the early 1980s [76,77,95] remains the most widely used linkage to date. Its facile introduction on the 3 -hydroxyl of the leader nucleoside [106] and the easy coupling of the resulting 3 -succinyl derivative to an amino-linked solid support [83,107,108] are favorable features that justified the widespread use of this linker. In addition, this linker provides a convenient deprotection protocol involving aqueous ammonia or a wide range of aUcylamines. 

A urethane linker, 40, was introduced by Sproat and Brown [109] as an alternative to the succinyl linkage and is prepared by reacting LCAA-CPG with tolylene-2,6-diisocyanate. A 19-mer oligonucleotide constructed on this urethane-linked CPG support was successfully deprotected by extended aqueous ammonia treatment at 56°C for 48 h. 

The following problem in energy transfer arises occasionally A thioester, such as succinyl-CoA, is available to a cell and the energy available in its unstable linkage is needed for synthesis of a different thioester. It would be possible for a cell to first form ATP or GTP,... 

One compound with high phosphoryl transfer potential, usually GTP, is generated from the cleavage of the thioester linkage in succinyl CoA. 

In this complex reaction catalyzed by succinyl-CoA synthase (succinate thiokinase), the energy-rich thioester linkage of succinyl-CoA is hydrolyzed with release of free energy that is conserved in the substrate phosphorylation of GDP with phosphate to form GTP ... 

Cystathionine y-synthase (CGS) is a rather unique PLP-enzyme that catalyzes a transsulfuration reaction important in microbial methionine biosynthesis. It is the only known enzyme whose function is the catalysis of a PLP-dependent replacement reaction at the y-carbon of the amino acid substrate the succinyl moiety of O-succinyl-L-homoserine is replaced by i-Cys to give the thioether linkage of L,/.-cystathionine (scheme II). In the absence of L-Cys, the enzyme catalyzes a net y-elimination reaction from OSHS (scheme II). Because both reactions require the elimination of succinate, the catalytic pathways must diverge from a common reaction intermediate. It was originally hypothesized that a vinylglycine quinonoidal intermediate (structure 11)... 

Carter, M.C., Meyerhoff, M.E., Instability of succinyl ester linkages in 02-monosuccinyl cyclic AMP-protein conjugates at neutral pH,... 

Figure 2-3 The catalytic mechanism of ALAS as proposed by Jordan [66], The reaction mechanism involves the formation of a Schiff base linkage between glycine and the PLP cofactor. Removal of the pio-R proton yields a carbanion which reacts with the second substrate, succinyl-CoA. Note the retention of the pro-5 proton of glycine in the pro-5 position of C-5 of ALA. ALA, 5-amino-levulinic acid.

Several strategies for increasing the permeability of the brain capillaries to proteins have been developed. The permeability of the BBB can be transiently increased by intra-arterial injection of the solutions with high osmolarity, which disrupts inter-endothelial tight junctions [11]. Certain protein modifications, such as cationization by hexamethyldiamine [12] and anionization by succinylation [13], produce enhanced uptake in the brain. Modification of drugs [14] and proteins [15] by linkage to an anti-transferrin receptor antibody also appears to enhance transport into the brain. This approach depends on receptor-mediated transcytosis of transferrin-receptor complexes by brain endothelial cells substantial uptake also occurs in the liver. 

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