Modified phosphorous intermediates for providing functional groups on the 5' end of oligonucleotides

US5726329A · kind A · utility

Assignee

• La Jolla Pharmaceuticals Company · US

Inventors

• David S. Jones · San Diego, US
• John P. Hachmann · San Diego, US
• Michael J. Conrad · Monroe, US
• Stephen Coutts · Rancho Santa Fe, US
• Douglas Alan Livingston · San Diego, US

Key dates

• Filing date: May 8, 1995
• Grant date: Mar 10, 1998
• Expiry date: May 8, 2015

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Phosphoramidites of the formula ##STR1## where R is a base-labile protecting group, R.sup.1 and R.sup.2 are individually alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, or aryl of 6 to 20 carbon atoms or are joined together to form with the nitrogen atom a cyclic structure of 4-7 carbon atoms and 0 to 1 annular chalcogen atoms of atomic number 8 to 16, G is a hydrocarbylene group of 1 to 20 carbon atoms and Z is a hydroxy-protected vicinal diol group bound to G by one of the vicinal diol carbon atoms or a disulfide group and bound to G by one of the sulfur atoms of the disulfide group, with the proviso that G is of at least 4 carbon atoms when Z is said disulfide group are used in conventional automated oligonucleotide synthesis to introduce a functional aldehyde or thiol group on the 5' end of the oligonucleotide to thereby provide a reactive site on the oligonucleotide that may be used to conjugate the oligonucleotide to molecules that contain a free amino group or an electrophilic center reactive with a thiol group.