Oligonucleotides possessing a primary amino group in the terminal nucleotide

• US 5,118,800 A
• Filed: 02/27/1991
• Issued: 06/02/1992
• Est. Priority Date: 12/20/1983
• Status: Expired due to Term

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Smith, Lloyd M., Fung, Steven, Kaiser, Robert J. Jr.
• Primary Examiner(s): Brown, Johnnie R.
• Assistant Examiner(s): Kunz, Gary L.
• Application Number:
  US07/661,914
• Time in Patent Office: 461 Days
• Field of Search: 536/27-29
• US Class Current: 536/23.1
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence

Abstract

The invention consists of compounds and methods for the synthesis of oligonucleotides which contain one or more free aliphatic amino groups attached to the sugar moieties of the nucleoside subunits. The synthetic method is versatile and general, permitting amino groups to be selectively placed at any position on oligonucleotides of any composition or length which is attainable by current DNA synthetic methods. Fluorescent dyes or other detectable moieties may be covalently attached to the amino groups to yield the corresponding modified oligonucleotide.

Claims

1. The oligonucleotide compound having the formula:

##STR26## wherein B is selected from the group consisting of a nucleoside base and their derivatives.

2. The compound of claim 1 wherein B is thymine.

3. The compound of claim 1 wherein B is uracil

11. The compound of any one of claims 1, 4, or 7 wherein B is selected from the group consisting of 6-chloropurine, 6-chloro-2-fluoropurine, 2,6-dihydroxyaminopurine, 8-bromoadenine, 2-chloroadenine, 8-azidoadenine, 8-mercaptoadenine, 8-aminoadenine, 6thioguanine, 2,6-dichloropurine, N,N-dimethyl-6-aminopurine, N⁶ -benzyladenine, 1,3dimethylxanthine, 2-amino-6,8-dihydroxypurine, 6-methoxypurine, 6-mercaptopurine, 6-(2-hydroxyethyl)-aminopurine, N⁶ -(2-isopentyl)-adenine, N⁶ -furfuryladenine (kinetin), 5-bromomethyluracil, 5-dibromomethyluracil, 5-hydroxymethyluracil, 5-formyluracil, 5-fluorouracil, 5-bromouracil, 6-methyl-2-thiouracil, 5-hydroxymethyl-6-methyluracil, 5-hydroxyuracil (isobarbituric acid), 5-methoxyuracil, 5-methylcytosine, 5-trifluoromethyluracil, 5-nitrouracil, 5-aminouracil, 2-thiocytosine, 2-amino-4,6-dihydroxypyrimdine, 4-amino-2,6-dihydroxypyrimidine, 2-amino-4-hydroxy-6-methylpyrimidine, or 4-amino-6-hydroxy-2-mercaptopyrimidine, and their derivatives.

4. The oligonucleotide compound having the formula:

##STR27## wherein B is selected from the group consisting of a nucleoside base and their derivatives.

5. The compound of claim 4 wherein B is uracil.

6. The compound of claim 4 wherein B is thymine.

7. The oligonucleotide compound having the formula:

##STR28## wherein B is selected from the group consisting of a nucleoside base and their derivatives.

8. The compound of claim 7 wherein B is thymine.

9. The compound of claim 7 wherein B is uracil.

10. The oligonucleotide compound having the formula:

##STR29## wherein B is selected from the group consisting of adenine, guanine, thymine, cytosine, uracil and inosine;

R1, R2 and R5 and H, OH or NH₂ with the proviso that one of R1, R2 and R5 is NH₂ and only R5 can be OH.