Track topics on Twitter Track topics that are important to you
Daunomycin (Dau) is a DNA-binding antineoplastic agent in the treatment of various types of cancer, such as osteosarcomas and acute myeloid leukemia. One approach to improve its selectivity and to decrease the side effects is the conjugation of Dau with oligopeptide carriers, which might alter the drug uptake and intracellular fate. Here, we report on the synthesis, characterization, and in vitro biological properties of a novel conjugate in which Dau is attached, via an oxime bond, to one of the cancer specific small peptides (LTVSPWY) selected from a random phage peptide library. The in vitro cytostatic effect and cellular uptake of Dau═Aoa-LTVSPWY-NH(2) conjugate were studied on various human cancer cell lines expressing different levels of ErbB2 receptor which could be targeted by the peptide. We found that the new daunomycin-peptide conjugate is highly cytostatic and could be taken up efficiently by the human cancer cells studied. However, the conjugate was less effective than the free drug itself. RP-HPLC data indicate that the conjugate is stable at least for 24 h in the pH 2.5-7.0 range of buffers, as well as in cell culture medium. The conjugate in the presence of rat liver lysosomal homogenate, as indicated by LC-MS analysis, could be degraded. The smallest, Dau-containing metabolite (Dau═Aoa-Leu-OH) identified and prepared expresses DNA-binding ability. In order to get insight on the potential mechanism of action, we compared the protein expression profile of HL-60 human leukemia cells after treatment with the free and peptide conjugated daunomycin. Proteomic analysis suggests that the expression of several proteins has been altered. This includes three proteins, whose expression was lower (tubulin β chain) or markedly higher (proliferating cell nuclear antigen and protein kinase C inhibitor protein 1) after administration of cells with Dau-conjugate vs free drug.
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University , Budapest, Hungary.
This article was published in the following journal.
Name: Bioconjugate chemistry
Design, synthesis and characterization of cyclic peptidomimetics of the inducible nitric oxide synthase (iNOS) binding epitope that disrupt the protein-protein interaction involving SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) and iNOS.
SPSB2 knock-out mice have been found to exhibit prolonged expression of iNOS in macrophage cells and enhanced killing of persistent pathogens, suggesting that inhibitors of SPSB2-iNOS interaction have...
We have synthesized two Re(CO)3-modified lysine complexes ( and ), where the metal is attached to the amino acid at the Nε position, via a one-pot Schiff base formation reaction. These compounds can ...
Chimeric proteins consisting of a targeting moiety and a cytotoxic moiety are now under intense research focus for targeted therapy of cancer. Here, we report cloning, expression, and purification of ...
Timely clearance of apoptotic cells is an important step in the resolution of ongoing inflammation and the restoration of tissue integrity and function after acute myocardial infarction. Natural produ...
Fullerene-peptides represent a simple yet chemically diverse example of a bio-nano conjugate. The C60 moiety provides the following attributes to the conjugate: (a) precise three-dimensional archi...
The present proposal is designed to examine the effect of carbohydrate and protein co-ingestion on muscle protein synthesis during endurance type exercise activities. We hypothesize that m...
The aim of the present study is to investigate the effect of added protein+leucine or caffeine to 1.2 g/kg/h CHO on the rate of post-exercise muscle glycogen re-synthesis in healthy, recre...
The investigators determined effects of 8-week dietary protein intake in mixed meals with uneven or even consumption pattern on the metabolic outcomes of whole-body net protein synthesis a...
This is a prospective in vitro cell biology study of polymorphonuclear leukocyte (PMN) protein synthesis in response to PAF. PMNs from cord blood of premature human infants at risk for NEC...
When we age, we lose muscle. It is not exactly clear why this happens, but we do know that this muscle loss can increase health risks and lead to health problems. Lifting weights (i.e. per...
Semisynthetic vaccines consisting of polysaccharide antigens from microorganisms attached to protein carrier molecules. The carrier protein is recognized by macrophages and T-cells thus enhancing immunity. Conjugate vaccines induce antibody formation in people not responsive to polysaccharide alone, induce higher levels of antibody, and show a booster response on repeated injection.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
The production of PEPTIDES or PROTEINS by the constituents of a living organism. The biosynthesis of proteins on RIBOSOMES following an RNA template is termed translation (TRANSLATION, GENETIC). There are other, non-ribosomal peptide biosynthesis (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT) mechanisms carried out by PEPTIDE SYNTHASES and PEPTIDYLTRANSFERASES. Further modifications of peptide chains yield functional peptide and protein molecules.
Protein factors uniquely required during the initiation phase of protein synthesis in GENETIC TRANSLATION.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...