Antibiotic used to select genetically-engineered cells
Phleomycin is a glycopeptide antibiotic.
Glycopeptide antibiotics, a class of agents of microbial origin, are composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include the anti-infective and antitumor antibiotics.
In vitro: Previous study found that the chromosomes could be cleaved into nucleosomes and degraded by phleomycin over significantly narrower dose ranges than by bleomycin. In addition, phleomycin also showed lower specificity for internucleosomal cleavage than bleomycin. Moreover, it was found that the higher reactivity of phleomycin did not solely result from its higher rate of internucleosomal and intranucleosomal chromatin cleavage, since short phleomycin reactions always led to more extensive chromatin cleavage at low concentrations [1].
In vivo: A study of the in-vivo effects of phleomycin on meiosis of the mouse egg demonstrated a spectrum of damage to both first metaphase and second metaphase with polar body. The minimal effective dose in vivo of 2.5 μg/g of body weight could alter 28.3% of first metaphase figures and 50% of second metaphase cells [2].
Clinical trial: So far, no clinical study has been conducted.
参考文献:
[1] Moore, C.?W. Internucleosomal cleavage and chromosomal degradation by bleomycin and phleomycin in yeast. Cancer Research 48(23), 6837-6843 (1988).
[2] Jagiello GM.? Action of phleomycin on the meiosis of the mouse ovum. Mutat Res. 1968 Sep-Oct;6(2):289-95.
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