METHOD OF PRODUCING PEPTIDE-NUCLEIC ACIDS OLIGOMERS, CONTAINING CARBOXYETHYL SUBSTITUTE IN α- OR γ-POSITION OF SIDE CHAIN Russian patent published in 2016 - IPC C07K1/04 C07K14/00 C07K19/00 

FIELD: biochemistry.

SUBSTANCE: invention relates to bioorganic chemistry, pharmacology, molecular biology and can be used for producing therapeutically significant polyamide mimetics of oligonucleotides (PNA), promising medicines of directed action with high stability in biological mediums. Method of producing peptide-nucleic acids oligomers is disclosed, which contain carboxyethyl substitute in α- or γ-position of side chain, consists in growth of polyamide sequence on polystyrene carrier, comprising α-carboxyethyl-substituted links of general formula -NH-(CH₂)₂N(COCH₂B)-CH[(CH₂)₂COOH]-CO- or γ-carboxyethyl-substituted links of general formula -NH-CH[(CH₂)₂COOH]-CH₂-N(COCH₂B)-CH₂-CO-, where B is purine or pyrimidine nucleic base, with subsequent treatment of carrier with mixture, based on trifluoroacetic acid and trifluoromethanesulfonic acid, wherein to increase output and simplify cleaning of target oligomers, namely reducing amount of by-products, carrier is preliminarily cooled to -45…-50 °C, and triisopropylsilane is added to mixture instead of m-cresol in volume ratio of reagents trifluoroacetic acid:trifluoromethanesulfonic acid:triisopropylsilane 8:1:1. Method allows to almost completely eliminate formation of by-products, associated with N-end regroupping of polyamide frame.

EFFECT: composition of end reaction mixture is considerably enriched with target PNA oligomer, which facilitates further purification by HPLC.

1 cl, 6 dwg, 3 ex