title: Synthesis and application of highly reactive amino linkers for functional oligonucleotides.
abstract: Oligonucleotides are functionalized by conjugation with a variety of molecules, and aliphatic amino linkers have been frequently used as a tether for their modifications. This unit describes the syntheses and applications of novel amino linkers having a carbamate structure. Two major chemical properties of the primary amine are induced by the neighboring effect of the carbamate group, which are found to be optimum in an aminoethyl carbamate structure. First, the hydrophobic monomethoxytrityl group can be rapidly removed from the aminoethyl carbamate under very mild acidic conditions, while the deprotection is not completed in standard aliphatic amines even under high acid concentration. This significant feature enables the convenient purification of amino-modified oligonucleotides by using the hydrophobic interaction of the monomethoxytrityl group with a reverse-phase resin. Second, the introduction of the carbamate linkage reduces the pK(a) value of the neighboring primary amine, resulting in an increase in the conjugation yields with various functional molecules, such as those having active esters. The novel amino linkers that have an aminoethyl carbamate linkage indicate potent activity and are applicable for the preparation of various functional oligonucleotides.
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Sapporo, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kojima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Komatsu
mesh_terms: D000586:Amination; D000588:Amines / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry; D004148:Dioxolanes / Q000737:chemistry; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C111381:1-chloromethylnaphthalene; D000588:Amines; D003432:Cross-Linking Reagents; D004148:Dioxolanes; D009281:Naphthalenes; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; C024356:2,2-dimethyl-1,3-dioxolane-4-methanol