Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.26.4 (
RNase H
)
2,751
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
This article reviews the authors' investigation of the enzyme
RNase H
(EC 3.1.4.34.) in human leukemic cells and presents the accumulated available data, based on which this enzyme is proposed to serve as a new biological parameter in the study of progression of human leukemias. The introduction gives a brief account of the occurrence, characterization and possible biological role of
RNase H
in cells and in retroviruses. The results reviewed briefly concern: (1) the development of a new convenient, economic and reliable assay for normal and leukemic blood mononuclear cell
RNase H
, which is capable of resolving subtle activity differences between samples; (2) the differentiation of
RNase H
levels between normal and leukemic cells; (3) the correlation of
RNase H
levels from different leukemia types with the severity of the disease; (4) the correlation of
RNase H
levels in leukemic cells with clonogenic stages in the clonal differentiation pathway; (5) the predictive potential of a
RNase H
activity-based parameter (phi) in assessing progression in acute myelocytic leukemia and (6) the possibility of differentiation of the
RNase H
levels between normal and leukemic cells via regulation of the enzyme activity at the level of antagonistic phosphorylations mediated by cAMP and
calmodulin
.
...
PMID:RNase H of human leukemic cells: a new biological parameter in the study of human leukemias (review). 217 71
An endogenous nuclear enzyme,
RNase H
, is an important component in determining the efficacy of antisense oligodeoxynucleotides (ODNs). In an effort to improve the potency of antisense ODNs, conjugates with three different nuclear targeting signal peptides were prepared. These short peptide sequences have been shown to facilitate transport of macromolecules into the nucleus of cells. Efficient chemistry for the synthesis of ODN-peptide conjugates is described. Reaction of 5'-aminohexyl-modified ODNs with iodoacetic anhydride gave pure iodoacetamide ODNs (IA-ODNs) in good yield. These electrophilic intermediates were reacted with thiol-containing peptides to give ODN-peptides in excellent yield and purity. The ODN-peptides were further characterized by proteolysis with trypsin. Thermal denaturation studies with ssDNA targets showed little effect of the 5'-peptide modifications on the hybridization properties of the ODN. The effect of the nuclear signal peptides on antisense potency was evaluated in the freshwater ciliate Paramecium. A 3'-hexanol-modified 24-mer antisense ODN, complementary to the mRNA for
calmodulin
, alters regulation of membrane ion channels and swimming behavior of these cells. A 2'-O-methyl analog of this ODN was inactive, thus providing evidence that this activity in Paramecium is mediated by
RNase H
. Antisense ODN-nuclear signal peptide conjugates were transfected into the cells by electroporation. Surprisingly, these conjugates showed no antisense effects in comparison to a 5'-unmodified control ODN. Random peptides or amino acids conjugated to the 5'-terminus did not decrease antisense activity.
...
PMID:Synthesis and evaluation of nuclear targeting peptide-antisense oligodeoxynucleotide conjugates. 771 Oct 95
