Fig 1.
Rearrangement of NGR peptides resulting in dual acting properties.
Fig 2.
Structure of the cyclic NGR peptides and their Dau conjugates.
Fig 3.
Synthesis of Dau-NGR peptide conjugates with disulfide bridge or thioether bond in the cycle.
Fig 4.
Synthesis of Dau-NGR peptide conjugates with amide bond in the cycle.
Fig 5.
Synthesis of the control Dau-DGR peptide conjugates with amide bond in the cycle.
Fig 6.
Characteristics of cyclic NGR peptide–daunomycin conjugates.
aHPLC column: Phenomenex AERIS Peptide 3,6 μm XB-C18 (250 x 4,6 mm); eluents 0.1% TFA/ water (A) and 0.1% TFA/CH3CN−water (80:20 v/v) (B); gradient 0 min 0% B, 5 min 0% B, 50 min 90% B; flow rate 1 mL/min; detection: 220 nm. bAverage molecular weight. cESI-MS: Bruker Daltonics Esquire 3000+ ion trap mass spectrometer.
Fig 7.
Chemostability of cyclic NGR peptide–daunomycin conjugates.
Fig 8.
Cytostatic/cytotoxic effect of cyclic NGR peptide–daunomycin conjugates.
aTests were carried out 4 times; btests were carried out 3 times; IC50 values were averaged; statistical significance was calculated using unpaired t-tests.
Fig 9.
Lysosomal degradation of daunomycin-conjugates after 6 h.
Fig 10.
Direct uptake of daunomycin-conjugates.
Normalized uptake values indicate the fold increase of the measured fluorescent units compared to the autofluorescence of empty cells.