Nucleobase modified neamines with a lysine as a linker, their inhibition specificity for TAR-Tat derived from HIV-1

Ryo Inoue; Kentarou Watanabe; Toyofusa Katou; Yasunori Ikezawa; Keita Hamasaki

doi:10.1016/j.bmc.2015.03.001

Nucleobase modified neamines with a lysine as a linker, their inhibition specificity for TAR-Tat derived from HIV-1

Bioorg Med Chem. 2015 May 1;23(9):2139-47. doi: 10.1016/j.bmc.2015.03.001. Epub 2015 Mar 7.

Authors

Ryo Inoue¹, Kentarou Watanabe¹, Toyofusa Katou¹, Yasunori Ikezawa¹, Keita Hamasaki²

Affiliations

¹ Shibaura Institute of Technology, Department of Applied Chemistry, Toyosu 3-7-5, Koto-ku, Tokyo 138-8548, Japan.
² Shibaura Institute of Technology, Department of Applied Chemistry, Toyosu 3-7-5, Koto-ku, Tokyo 138-8548, Japan. Electronic address: hamie@shibaura-it.ac.jp.

PMID: 25819332
DOI: 10.1016/j.bmc.2015.03.001

Abstract

Nucleobase modified neamines with a lysine as the linker (NbK-neamines) were synthesized and their binding toward hairpin RNAs derived from HIV-1 activator region were studied. NbK-neamines were bind those RNAs with micro molar level of binding affinities and compete with corresponding activator peptide for TAR RNA, but not for RRE RNA. GbK-neamine denotes the highest binding affinity with TAR RNA, three to five times higher than other three NbK-neamines. GbK-neamine could be a candidate of potential inhibitor for TAR-Tat.

Keywords: Aminoglycoside; Neamine; Nucleobase; Potential inhibitor; RRE RNA; TAR RNA.

MeSH terms

Adenine / chemistry
Cytosine / chemistry
Framycetin / chemical synthesis
Framycetin / chemistry*
Framycetin / pharmacology*
Guanine / chemistry
HIV Long Terminal Repeat / drug effects*
HIV-1 / chemistry*
HIV-1 / genetics*
Lysine / chemistry*
Molecular Structure
Structure-Activity Relationship
Thymine / chemistry
tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*

Substances

tat Gene Products, Human Immunodeficiency Virus
Framycetin
neamine
Guanine
Cytosine
Adenine
Lysine
Thymine