Novel amino linkers enabling efficient labeling and convenient purification of amino-modified oligonucleotides.
We developed new amino linker reagents for an oligonucleotide (ONT) terminus. These reagents consist of an aminoethyl carbamate main linkage and a side-chain residue, which was a naphthylmethoxymethyl, methoxymethyl, or methyl group or a hydrogen atom. The primary amine was protected with a monomethoxytrityl (MMT) group. The chemical properties of ONTs containing these amino-modifications were investigated. The MMT group of these amino-modifications could be quite rapidly removed from the amine under very mild acidic conditions, which are not strong enough for the deprotection of a conventional aliphatic amine. This significant feature enabled the amino-modified ONTs to be conveniently purified with a reverse phase column. Furthermore, the amino-modifications efficiently reacted to active esters, as compared with other amino-modifications. We also found that the pK(a) values of the amino-modifications were lower than that of the aliphatic amine. All of the experimental results showed that these chemical properties are closely related to their structures. We report here the chemical properties and the availability of the new amino linker reagents.
Komatsu
Yasuo
Y
Research Institute of Genome-based Biofactory, National Institute of Advanced Industrial Science & Technology (AIST Hokkaido), 2-17-2-1 Tsukisamu-Higashi, Toyohira-ku, Sapporo 062-8517, Japan. komatsu-yasuo@aist.go.jp
Kojima
Naoshi
N
Sugino
Maiko
M
Mikami
Akiko
A
Nonaka
Ken
K
Fujinawa
Yumi
Y
Sugimoto
Takashi
T
Sato
Kousuke
K
Matsubara
Kenichi
K
Ohtsuka
Eiko
E
D000588:Amines / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D015394:Molecular Structure; D015345:Oligonucleotide Probes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
D000588:Amines; D015345:Oligonucleotide Probes; D009841:Oligonucleotides