scholarly journals Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

2018 ◽  
Vol 14 ◽  
pp. 911-918 ◽  
Author(s):  
Andrea Angelo Pierluigi Tripodi ◽  
Szilárd Tóth ◽  
Kata Nóra Enyedi ◽  
Gitta Schlosser ◽  
Gergely Szakács ◽  
...  

Cyclic NGR peptides as homing devices are good candidates for the development of drug conjugates for targeted tumor therapy. In our previous study we reported that the Dau=Aoa-GFLGK(c[KNGRE]-GG-)-NH2 conjugate has a significant antitumor activity against both CD13+ HT-1080 human fibrosarcoma and CD13− but integrin positive HT-29 human colon adenocarcinoma cells. However, it seems that the free ε-amino group of Lys in the cycle is not necessary for the biological activity. Therefore, we developed novel cyclic NGR peptide–daunomycin conjugates in which Lys was replaced by different amino acids (Ala, Leu, Nle, Pro, Ser). The exchange of the Lys residue in the cycle simplified the cyclization step and resulted in a higher yield. The new conjugates showed lower chemostability against deamidation of Asn than the control compound, thus they had lower selectivity to CD13+ cells. However, the cellular uptake and cytotoxic effect of Dau=Aoa-GFLGK(c[NleNGRE]-GG-)-NH2 was higher in comparison to the control especially on HT-29 cells. Therefore, this conjugate is more suitable for drug targeting with dual targeting property.

2008 ◽  
Vol 102 (2) ◽  
pp. 207-214 ◽  
Author(s):  
Paola Palozza ◽  
Diana Bellovino ◽  
Rossella Simone ◽  
Alma Boninsegna ◽  
Francesco Cellini ◽  
...  

Lycopene β-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of β-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced β-carotene release and therefore cell growth inhibition. To induce with purified β-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that β-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with β-carotene in promoting cell growth arrest.


2001 ◽  
Vol 172 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Giuseppe Cassano ◽  
Nicoletta Resta ◽  
Giuseppe Gasparre ◽  
Claudio Lippe ◽  
Ginevra Guanti

2021 ◽  
Vol 17 (74) ◽  
pp. 367
Author(s):  
Jianping Zhao ◽  
Zhenyu Feng ◽  
Shuang Meng ◽  
Xiaorong Zhou ◽  
Xiaojuan Ma ◽  
...  

2003 ◽  
Vol 24 (8) ◽  
pp. 1369-1378 ◽  
Author(s):  
C. Chen ◽  
G. Shen ◽  
V. Hebbar ◽  
R. Hu ◽  
E. D. Owuor ◽  
...  

2000 ◽  
Vol 152 (2) ◽  
pp. 217-222 ◽  
Author(s):  
Giuseppe Cassano ◽  
Giuseppe Gasparre ◽  
Francesco Susca ◽  
Claudio Lippe ◽  
Ginevra Guanti

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