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New daunomycin–oligoarginine conjugates: Synthesis, characterization, and effect on human leukemia and human hepatoma cells
Author(s) -
Miklán Zsanett,
Orbán Erika,
Csík Gabriella,
Schlosser Gitta,
Magyar Anna,
Hudecz Ferenc
Publication year - 2009
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21264
Subject(s) - chemistry , characterization (materials science) , conjugate , leukemia , combinatorial chemistry , biochemistry , nanotechnology , medicine , mathematical analysis , mathematics , materials science
In this article, the synthesis, a novel chromatographic procedure and characteristics of a new class of daunomycin (Dau)–oligoarginine conjugates are described. In these compounds oligoarginine with 6 or 8 residues (Arg n , n = 6, 8) is attached to Dau by different covalent bond: squaric amide (Dau‐□‐Arg n ), oxime (DauNOCH 2 COArg n ), or hydrazone (HGlu(Arg n )NHNDau). Conjugates were characterized by RP‐HPLC and mass spectrometry. We report also on our findings concerning chemical and biological properties of Dau‐conjugates as a function of covalent linkage, site of conjugation and length of the oligoarginine moiety. Stability, fluorescent properties as well as cytostatic effect and cellular uptake of these compounds were studied. Dau‐conjugates with squaric amide or oxime linkage were stable, but continuous release of free Dau was observed from the hydrazone conjugate in solution. We found that some spectral characteristics (e.g., the amplitude of the emission spectrum) of conjugates could be sensitive for the site of coupling (amino vs. oxo function). Cytostasis and cellular uptake of conjugates were investigated both on human leukemia (HL‐60) and human hepatoma (HepG2) cell lines by MTT assay and flow cytometry We found that cytostatic effect and uptake properties of Dau‐conjugates were dependent on the acid stability of the linkage (hydrazone vs. oxime/amide) applied and more markedly on the cell line studied. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 489–501, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com