Serum stability

The 1,2,4-thiadiazole moiety has been incorporated in (3-lactam antibacterials to modulate pharmacokinetic properties and more recently into a cephalosporin. The cephalosporin 129 displays a good balance of serum stability and in vitro activity. The cephalosporin derivative 48 (see Section 5.08.7.4) also shows good pharmacokinetic properties <2001JAN364>. 

Figure 4 Effect on the serum stability of the incorporation of 5% cholesterol poly(ethy-lene glycol) (PEG) into cationic lipoplexes [hpopolyamine RPR209120/DOPE1/1, ratio (mol) lipid/DNA = 10 in 150 mM NaCl]. Lipoplexes were incubated in DMEM + 10% SVF, at 37°C, aliquots were regularly sampled and monitored by dynamic diffusion. Results represent a mean between three measurements. Error bars are not presented to simplify the graph, but differences among PEG, PEG-1, and PEG-2 are significant. Abbreviations PEG, poly(ethylene glycol) DOPE, dioleylphosphatidylethanolamine DMEM, Dulbecco s Modified Eagle Medium.

Zhang Y, Anchordoquy T. The role of lipid charge density in the serum stability of cationic lipid/DNA complexes. Biochim Biophys Acta 2004 1663 143. 

Cyclic peptides are important biologically active compounds that combine peptide properties with conformational bias and often improved serum stability and membrane penetration [1-3]. Depsipeptides are similar compounds, but they contain as part of their backbone one or more hydroxylated amino acid residues that add ester or lactone moieties to the peptide (Fig. 1) [4-6]. Cyclo- and... 

A number of modified nucleotides have been tested and described in siRNA design. These are mostly modifications of the 2 OH group of the ribose. By the incorporation of chemically modified nucleotides into siRNAs, the on-target efficiency of the siRNAs can be increased (42 4). On the other hand, different types of siRNA off-target effects can be reduced by the use of chemically modified nucleotides immunostimulatory effects (reviewed in (20)) as well as sequence-dependent miRNA-like off-target effects (26, 44,45) and passenger strand incorporation (46, 47). In addition, chemical modifications can be used to improve the cellular delivery of siRNAs in living animals and are important tools to enhance the serum stability of siRNAs (48). 

Bello-Roufai, M. and Midoux, P. (2001) Histidylated polylysine as DNA vector elevation of the imidazole protonation and reduced cellular uptake without change in the polyfection efficiency of serum stabilized negative polyplexes. Bioconjug. Chem., 12, 92-99. 

These polymers have been designed to achieve serum stability and sustained circulation with the PEGylated peptide, specific targeting to hepatocytes with... 

Key Words Peptide degradation peptide-serum stability peptide half-life. 

In a general serum stability assay, the peptide is subjected to human serum (see Note 3) at realistic temperature conditions and incubated for various time intervals, comparable to traditional protease assays. The reactions are stopped by TCA or ethanol, precipitating larger serum proteins while leaving peptides... 

Several factors are known to inflict on the peptides serum stability, causing misleading results ... 

Otvos, L., Jr., Cappelletto, B., Varga, I., et al. (1996) The effects of post-translational side-chain modifications on the stimulatory activity, serum stability and conformation of synthetic peptides carrying T helper cell epitopes. Biochim. Biophys. Acta 1313, 11-19. 

Each immunotoxin is evaluated in a series of stages. These include assessment of specificity, cytotoxicity, and serum stability selection of a relevant animal species and route of drug administration and finally safety evaluation. 

Serum stability is another important attribute of immunotoxins as each immunotoxin must be sufficiently stable to progress from the blood into the tissues and be capable of penetrating into a tumor in a sufficient concentration to result in tumor cell death [8,12], Examination at 37 °C showed that VB4-845 was a stable immunotoxin [12],... 

Although extensive in vitro testing is performed on each immunotoxin to assess its cytotoxicity and specificity, it is animal model studies that ultimately determine the serum half-life, serum stability, as well as the efficacy of an immunotoxin. A compilation of the in vitro and in vivo data enables a decision to be made on the potential of each immunotoxin to be an effective and safe therapeutic and to determine whether human clinical trials are warranted. 

While acychc polyaminocarboxylate (DTPA, ethylenedi-aminetetraacetic acid (EDTA)) complexes of copper(n) have high thermodynamic stabihty, these complexes are kinetically labile to ligand exchange. Cu(ll) has been found to have much greater kinetic stability (and consequently greater serum stability) with macrocyclic chelates, such as TETA and DOTA,... 

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