Back to Search
Start Over
Peptide T-AraC Conjugates. Solid Phase Synthesis and Biological Activity of N4-(acylpeptidyl)-AraC
- Publication Year :
- 2000
-
Abstract
- Due to the capability of peptidyl derivatives of araC to behave as prodrugs of this antimetabolite, and because of the well known biological properties of peptide T and its analogues (in particular that of targeting CD4+ cells), new peptide T-araC conjugates were prepared and tested in vitro for antiproliferative activity. The aim was that of specifically delivering the antitumor drug to CD4+ cells. N4-(Acylpeptidyl)-derivatives of araC were synthesized by a new general approach involving solid-phase synthesis, which allows mild conditions, avoids the usually required protection of the glycoside portion of nucleosides and affords high yields of the final products. After the demonstration that peptide T-araC conjugates were able to activate chemotaxis by binding CD4 receptor on monocyte membranes, the antiproliferative activity was evaluated against a panel of leukemia lymphoma and carcinoma cell lines derived from human tumors, three CD4+ cell lines included. Title compounds resulted effective as antiproliferative agents at concentrations 4- to 10-fold higher than those of araC alone, did not preferentially inhibit CD4+ cells and proved stable not only in cell culture medium containing 20% FCS, but also in human plasma. All this suggests their potential utility in vivo.
- Subjects :
- Antimetabolites, Antineoplastic
Time Factors
Clinical Biochemistry
Pharmaceutical Science
Peptide
Biochemistry
Monocytes
chemistry.chemical_compound
Inhibitory Concentration 50
Solid-phase synthesis
Drug Stability
In vivo
Drug Discovery
Peptide synthesis
Tumor Cells, Cultured
Humans
Prodrugs
Molecular Biology
chemistry.chemical_classification
Drug Carriers
Dose-Response Relationship, Drug
Chemotaxis
Organic Chemistry
Cytarabine
Peptide T
Biological activity
In vitro
carbohydrates (lipids)
chemistry
Cell culture
CD4 Antigens
Molecular Medicine
Oligopeptides
Cell Division
Peptide Hydrolases
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....383dcd054b073a256580bdfe7c46ecd1