Target molecules, other, poly

We also examined the effect of duration of exposure to SAB on the enhancement we observed. Following treatment with alkylating agents, target molecules for poly-(ADP-ribosylation) are both ribosylated and deribosylated quite rapidly. If the biologic effects of SAB were quite rapid one might expect 4 h of exposure to yield as great an effect as 24 or 72 h, on the other hand, if one supposed a slow cumulative effect one... 

Preclinical Results Obtained with Particles. Poly-L-lysine and poly-L-Ornithine were used to generate particles that can entrap pDNA. The cationic polymers can be coupled to a targeting molecule such as galactose or mannose for enhanced delivery to the liver after intravenous or intraportal injections in mice [102-104]. Expression in other organs than the liver (for example, kidneys) is observed however, expression in the liver using these particles is dominant. Such particles are found to be more efficient and to persist for a longer time in the circulation than liposomes. Hepatic expression of the pDNA delivered by poly-L-Lysine particles can be found several months after delivery [105]. These promising formulations were not evaluated in humans. 

One example are magnetic nanoparticles [9], which have to be coated with a polymer layer (e.g., poly(ethylene glycol) (PEG), dextran, poly(vinyl pyr-rolidone) (PVP), fatty acids, polypeptides, chitosan, gelatin, etc.) in order to protect them and adjust their solubility as well as retention time in the body. The polymer layer also serves as a platform for the attachment of targeting molecules, therapeutics, or other imaging tags (Fig. 2.9). 

H. Other Target Molecules of the Poly(ADP-rlbose) Synthetase... 

Microspheres and nanoparticles often consist of biocompatible polymers and belong either to the soluble or the particle type carriers. Besides the aforementioned HPMA polymeric backbone, carriers have also been prepared using dextrans, ficoll, sepharose or poly-L-lysine as the main carrier body. More recently alginate nanoparticles have been described for the targeting of antisense oligonucleotides [28]. As with other polymeric carrier systems, the backbone can be modified with e.g. sugar molecules or antibody fragments to introduce cellular specificity. 

Reverse transcription PCR (RT-PCR) is a modification of the standard PCR technique that can be used to amplify mRNA. The first step is to convert isolated mRNA to a complementary DNA (cDNA) molecule using an RNA-dependent DNA polymerase (also known as reverse transcriptase) during a process called reverse transcription (RT). The complementary DNA can be used as any other DNA molecule for PCR amplification. The primers used for cDNA synthesis can be either nonsequence-specific primers (a mixture of random hexa-mers or oligo-dT primers) or sequence-specific primers (Fig. 2.4). Random hexamers are a mixture of all possible combinations of six nucleotide sequences that can attach randomly to mRNA and initiate reverse transcription of the entire RNA pool. Oligo-dT primers are complementary to the poly-A tail of mRNA molecules and allow synthesis of cDNA only from mRNA molecules. Sequence-specific primers are the most restricted because they are designed to bind selectively to mRNA molecules of interest, which makes reverse transcription a target-specific process. 

ADP-ribosyltransferases catalyze the formation of an ADP-ribosyl bond to a specific amino acid residue on a target protein or other acceptor molecule. The covalent modification then alters the activity or function of the target protein. This class of proteins includes bacterial toxins, bacterial activating proteins, endogenous ADP-ribosyltransferases, and the eukaryotic poly(ADP-ribose) synthase. 

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