Linked Life Data

9258444

Source:http://linkedlifedata.com/resource/pubmed/id/9258444

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-10-10
pubmed:abstractText
DNA therapeutics show great potential for gene-specific, nontoxic therapy of a wide variety of diseases. The deoxyribose phosphate backbone of DNA has been modified in a number of ways to improve nuclease stability and cell membrane permeability. Recently, a new DNA derivative with an amide backbone instead of a deoxyribose phosphate backbone, peptide nucleic acid (PNA), has shown tremendous potential as an antisense agent. Although PNAs hybridize very strongly and specifically to RNA and DNA, they are taken up by cells very poorly, limiting their potential as nucleic acid binding agents. To improve cellular uptake of a PNA sequence, it was conjugated to a D-amino acid analog of insulin-like growth factor 1 (IGF1), which binds selectively to the cell surface receptor for insulin-like growth factor 1 (IGF1R). The IGF1 D-peptide analog was assembled on (4-methylbenzhydryl)amine resin, and then the PNA was extended as a continuation of the peptide. The conjugate and control sequences were radiolabeled with 14C or fluorescently labeled with fluorescein isothiocyanate. Cellular uptake of the PNA-peptide conjugate, a control with two alanines in the peptide, and a control PNA without the peptide segment were studied in murine BALB/c 3T3 cells, which express low levels of murine IGF1R, in p6 cells, which are BALB/c 3T3 cells which overexpress a transfected human IGF1R gene, and in human Jurkat cells, which do not express IGF1R, as a negative control. The specific PNA-peptide conjugate displayed much higher uptake than the control PNA, but only in cells expressing IGF1R. This approach may allow cell-specific and tissue-specific application of PNAs as gene-regulating agents in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1043-1802
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
481-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:articleTitle
Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake.
pubmed:affiliation
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.