Reagents for the preparation of 5'-biotinylated oligonucleotides

• US 4,908,453 A
• Filed: 01/23/1989
• Issued: 03/13/1990
• Est. Priority Date: 01/23/1989
• Status: Expired due to Term

• Current Assignee: PerkinElmer Life Sciences, Inc.
• Original Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Inventors: Cocuzza, Anthony J.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US07/300,504
• Time in Patent Office: 414 Days
• Field of Search: 540/450, 540/454, 540/455, 540/460, 540/461, 540/542, 544/50, 544/52, 544/54, 544/57, 544/90, 544/133, 544/150, 544/243, 544/244, 544/337, 546/21, 548/113
• US Class Current: 548/113
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• 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

Abstract

Reagents useful in the preparation of 5'"'"'-biotinylated oligonucleotides are disclosed.

Claims

1. A chemical compound of the formula

View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)

2. A compound according to claim 1 wherein SG is --(CH₂)_r --X--;

r=2-3;

X is selected from the group consisting of --CH₂ --, --X¹ L--, and ##STR27## X¹ is selected from the group consisting of --CH₂ O--, --CH₂ S--, ##STR28## R and R¹ are as defined above; and

R⁵ is selected from the group consisting of ##STR29## and alkyl-substituted derivatives thereof;

t=0-10; and

L is selected from the group consisting of substituted and unsubstituted derivatives selected from the group consisting of C_2-20 alkylene wherein the alkylene segment may contain one or more groups selected from the group consisting of arylene, cycloalkylene, heterocyclene, ether, thioether, sulfone, sulfoxide, amide, ureido, keto, and dithio;

C_3-8 cycloalkylene;

C_4-20. alkylenecycloalkyl;

C_6-10 arylene;

##STR30## wherein z=1-10;

C_7-20 arylalkylene; and

3-10 membered ring aromatic or alicyclic heterocyclenes wherein the heteroatom(s) may be selected from the group Consisting of N, O, and S.

3. A compound according to claim 2 wherein r is 2, X is --CH₂ --, and A is --CH₂ --.

4. A compound according to claim 2 wherein r is 3.

5. A compound according to claim 4 wherein X is --CH₂ --.

6. A compound according to claim 4 wherein A is --O--.

7. A compound according to claim 6 wherein X is --CH₂ --.

8. A compound according to claim 6 wherein X is ##STR31##

9. A compound according to claim 6 wherein X is --X¹ --L--, X¹ is ##STR32## and R is selected from the group consisting of H, C_1-4 unbranched alkyl, and C_3-5 branched alkyl.

10. A compound according to claim 9 wherein R is selected from the group consisting of H and CH₃.

11. A compound according to claims 3, 5, 7, 8, or 10 wherein Q is selected from the group consisting of ##STR33##

12. A compound according to claim 11 wherein Y is selected from the group consisting of 4--Cl--C₆ H₄ --O--;

2--Cl--C₆ H₄ --O--;

4--NO₂ --C₆ H₄ --O--;

4--NO₂ --C₆ H₄ CH₂ CH₂ l --O--;

2,4--NO₂ --C₆ H₃ CH₂ CH_2--O--;

2,4-Cl₂ --C₆ H₃ --O--;

2,3-Cl₂ --C₆ H₃ --O--;

NCCH₂ CH₂ O--;

NCCH₂ C(CH₃)₂ --O--;

CH₃ O--;

(Z)₃ CCH₂ --O--;

(Z)₃ CC(CH₃)₂ --O--R'"'"'S--;

R'"'"'SCH₂ CH₂ --O--;

R'"'"'SO₂ CH₂ CH₂ --O--; and

R'"'"'NH--, wherein Z is selected from the group consisting of Cl, Br, and I, and R'"'"' is selected from the group consisting of H, C_3-1 branched alkyl, C_1-10 unbranched alkyl, C_6-10 aryl, C_7-12 alkaryl, and C_7-12 aralkyl.

13. A compound according to claim 12 wherein Q is ##STR34## and R² and R³ are --CH(CH₃)₂.

14. A compound according to claim 13 wherein Y is selected from the group consisting of NCCH₂ CH₂ O-- and CH₃ O--.

15. A compound according to claim 14 wherein R is H and L is C_2-20 alkylene.

16. A compound according to claim 15 wherein L is selected from the group consisting of --(CH₂)₂ -- and --(CH₂)₃ --.

17. A compound according to claim 14 wherein R is H and L is 1,4-cyclohexylene.

18. A compound according to claim 14 wherein R is H, L is ##STR35## and v=1-10.

19. A compound according to claim 18 wherein L is ##STR36##

20. A compound according to claim 14 wherein

R is H,L is ##STR37## v is 1-10 and w is 1-10.