Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.

Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes or nucleic acids. Polylysine based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study we report on our findings on the cellular uptake characteristics of nine structurally related polylysine based

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Pitfalls in the synthesis of fluorescent methotrexate containing oligopeptide conjugates M. Sebestyen et al. a) Unexpected cyclopeptide-formation with the lactonecarboxylic group of the Cf was detected, when Cf was attached to the α-amino group of the Lys residue on solid phase. This was avoided by changing the order of Cf incorporation with using Fmoc/Dde strategy. Alternatively, we have built the peptide with Fmoc strategy on solid phase first and performed the labelling with Cf-OSu subsequently in solution. Pitfalls in the synthesisb) During HF cleavage of the protected conjugates, MTX was demonstrated to form adducts with anisole and p-cresol scavengers, and the TMSOTf cleavage methodology was also found to be inadequate due to the large number of side products formed. We report here that using Fmoc/Dde strategy is an appropriate method to circumvent the cleavage with HF or TMSOTf. c) During the coupling of MTX with oligopeptide, structural and stereo isomers are formed. We have described here the suitable conditions of HPLC separation of these products. † Abbreviations: a: D-alanine, A: L-alanine