期刊
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
卷 -, 期 -, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/bbb/zbad128
关键词
protein kinase C; aplysiatoxin; human immunodeficiency virus (HIV); acquired immunodeficiency syndrome (AIDS); shock and kill
The phosphate ester of 10-methyl-aplog-1, known as phos-10MA-1, shows similar biological activity with 10MA-1 in vitro and has the potential to reactivate latent HIV for HIV eradication strategy.
10-Methyl-aplog-1 (10MA-1), a simplified analog of aplysiatoxin, exhibits a high binding affinity for protein kinase C (PKC) isozymes with minimal tumor-promoting and pro-inflammatory activities. A recent study suggests that 10MA-1 could reactivate latent human immunodeficiency virus (HIV) in vitro for HIV eradication strategy. However, further in vivo studies were abandoned by a dose limit caused by the minimal water solubility of 10MA-1. To overcome this problem, we synthesized a phosphate ester of 10MA-1, 18-O-phospho-10-methyl-aplog-1 (phos-10MA-1), to improve water solubility for in vivo studies. The solubility, PKC binding affinity, and biological activity of phos-10MA-1 were examined in vitro, and the biological activity was comparable with 10MA-1. The pharmacokinetic studies in vivo were also examined, which suggest that further optimization for improving metabolic stability is required in the future. Graphical Abstract A phosphate ester of 10-methyl-aplog-1 was evaluated biologically as a possible latency-reversing agent for human immunodeficiency virus reactivation in vitro.
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