Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protamine sulfate enhanced transfection of Streptococcus pneumoniae by DNA of omega 3 phage by factors as large as 10(5)-fold, provided it was present at the time the cells were added to the DNA. For DNA concentrations well below 1 microgram/ml, the optimum amount of protamine sulfate was near 1 microgram/ml of cells. Higher DNA concentrations required more protamine for maximum effect, and in all cases transfection fell when protamine was in excess. Transformation was not enhanced by low protamine levels and was inhibited by higher levels. A recipient strain with low but finite endonuclease activity and normal transformability showed higher transfection than did the wild type at low DNA concentrations but less than did the wild type at high DNA concentrations. Protamine sulfate enhanced its transfection at low, but not high, DNA concentrations. The behavior of this strain and the enhancement of transfection by protamine sulfate of wild-type cells were each consistent with less cutting of the donor DNA at the cell surface, which is part of the normal entry process in naturally competent gram-positive bacteria. Less cutting would lead to entry of fewer but longer strands that would be more efficient in reconstruction of the 33-megadalton phage replicon. We suggest that in this system protamine enhances transfection by inhibition of the surface nuclease action that is part of the normal entry process.
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PMID:Enhancement of pneumococcal transfection by protamine sulfate. 713 Jan 29

Presystemic degradation in the gastrointestinal tract is one of the major problems contributing to the poor oral absorption of antisense oligonucleotides. Complexes between the antisense phosphorothioate oligodeoxynucleotide ISIS 2302 and the polycationic carriers protamine sulfate grade X, protamine chloride grade V, protamine phosphate grade X, poly-L-lysine hydrobromide (PLL), spermidine phosphate salt, spermine diphosphate salt, and Protasan G113 and CL113 were formulated in order to increase stability against intestinal nucleolytic degradation. Specific conductivity measurements were carried out to determine the charge ratio of the complex systems. Nuclease stability assays were performed in a rat small intestine homogenate model, which displayed significant exo- and endonuclease activity. Full-length oligonucleotide and metabolites were analyzed by capillary gel electrophoresis with UV detection at 260 nm. Most of the complexes of ISIS 2302 and the polycationic materials, except PLL-based systems, showed a better protection against enzymatic metabolism than free oligonucleotide. Protamine sulfate and protamine chloride considerably enhanced the nuclease stability of the phosphorothioate antisense oligonucleotide. The association of oligonucleotides with several polycationic substances proved to be an alternative to chemical modification in order to stabilize oligonucleotides in the gastrointestinal tract against nucleolytic degradation.
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PMID:Stability of polycationic complexes of an antisense oligonucleotide in rat small intestine homogenates. 1255