Folic acid conjugates of a bleomycin mimic for selective targeting of folate receptor positive cancer cells

A major challenge in the application of cytotoxic anti-cancer drugs is their general lack of selectivity, which often leads to systematic toxicity due to their inability to discriminate between malignant and healthy cells. A particularly promising target for selective targeting are the folate receptors (FR) that are often over-expressed on cancer cells. Here, we report on a conjugate of the pentadentate nitrogen ligand N4Py to folic acid, via a cleavable disulphide linker, which shows selective cytotoxicity against folate receptor expressing cancer cells.     

Cytokinin conjugation: recent advances and patterns in plant evolution

Cytokinin (CK) conjugates are important in plant development because they regulate active CK concentrations, CK transport, storage, and irreversible inactivation. While numerous CK conjugates have been identified in higher plants, the biological functions of these compounds, their location within cells and tissues, and the enzymes and genes involved in their regulation are not clearly understood. In this paper, recent advances are reported which have occurred through the study of transgenic plants containing the ipt or rolC genes, the identification of new regulatory enzymes affecting CKs, and the characterization of new CK conjugates. In addition, a survey of the literature is presented which examines the pattern of CK conjugates found in different plant taxa. Based on current knowledge, it appears that green algae, mosses, and ferns contain relatively few CK conjugates of isopentenyl adenine (iP) and zeatin (Z). In contrast, higher land plants, such as gymnosperms and angiosperms, contain a more complex set of CKs, primarily conjugates of Z and dihydrozeatin (DHZ). This suggests that the pattern of CK conjugation has become more complex in parallel with the increasing complexity of higher plants.     

Synthetic peptides as carriers for cellular import of drugs

Summary We describe the solid phase synthesis of an amphipathic peptide C-terminated by a cysteamide group which allows further addition after removal from the resin and cleavage of the side-chain protecting groups. The peptide is shown to be rapidly internalized by cells with a nuclear localization of the peptide. When the peptide is linked to an oligonucleotide, the conjugate is also internalized with a final localization that is mainly cytoplasmic.     

Molecular cloning and expression of a cDNA for human kidney cysteine conjugate β-lyase

Kidney cysteine conjugate β-lyase (glutamine transaminase K, kyneurenine aminotransferase, EC 2.6.1.64) metabolises the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites which can produce nephrotoxicicity and neurotoxicicity in experimental animals and man. Using a combination of hybridisation screening and PCR techniques we have isolated a full-length cDNA for human kidney cysteine conjugate β-lyase. Comparison of the deduced amino acid sequence with that of the rat enzyme indicated an 82% overall similarity, with 90% similarity around the pyridoxal phosphate binding site, many of the changes being conservative in nature. Expression of the cDNA in Cos-1 cells resulted in the production of a cytosolic enzyme which showed both cysteine conjugate β-lyase and glutamine transaminase K activity. Preliminary mapping of the gene for human cysteine conjugate β-lyase by PCR analysis of genomic DNA from human-rodent hybrid cells indicated that it is located on human chromosome 9.