Hydrazide building blocks and hydrazide modified biomolecules

• US 7,129,229 B2
• Filed: 08/10/2001
• Issued: 10/31/2006
• Est. Priority Date: 08/11/2000
• Status: Expired due to Fees

• Current Assignee: Sanofi-Aventis SA (Sanofi )
• Original Assignee: Nanogen Recognomics GmbH
• Inventors: Greef, Charles H., Raddatz, Stefan, Brücher, Christoph, Müller-Ibeler, Jochen, Windhab, Norbert, Havens, John R., Wang, Daguang, Onofrey, Thomas J., Schweitzer, Markus
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US10/344,092
• Publication Number:
  US 20040087807A1
• Time in Patent Office: 1,908 Days
• Field of Search: 558/70, 558/166, 558/162, 558/185, 558/183, 558/181, 558/180, 558/116, 558/117, 514/114, 514/115
• US Class Current: 514/114
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: C07F 9/2408 of hydroxyalkyl compounds
• CPC Class Codes: C07F 9/2429 of arylalkanols

Abstract

This invention relates to attachment chemistries for binding macromolecules to a substrate surface or to other conjugation targets. More particularly, this invention relates to attachment chemistries involving branched or linear structures having one or more hydrazide attachment moieties for binding the macromolecules to a substrate surface, or for other conjugation reactions. Novel modifying reagents are provided for the introduction of protected hydrazide attachment moieties or precursor forms of such hydrazides to the macromolecule, either as a single hydrazide or as multiple hydrazides.

Claims

1. A compound of the general formula:

P_r—

O-L_a-Bz-(CONHNH-P_Ga)_m

wherein;

Bz is a benzene ring,

L_a is a branched or unbranched hydrocarbon of 1 to 12 carbons, arid L_a may optionally include 1 to 4 ether or amide linkages between the carbons;

P_r is a phosphorous bearing reactive group selected from the group consisting of

2. The compound of claim 1 wherein each P_Ga is, independently, selected from the group consisting of trityl, methyltrityl, monomethoxytrityl, and dimethoxytrityl.

3. The compound of claim 1 wherein L_a is (CH₂)_n, wherein n is an integer between 1 and 12.

4. The compound of claim 1, wherein R_a and R_b are isopropyl and R_c is 2-cyanoethyl.

5. The compound of claim 1 with the general formula:

6. The compound of claim 1 with the general formula:

7. The compound of claim 1, wherein P_r—

O-L_a-Bz-(CONHNH-P_Ga)_m is selected from the group consisting of 5-[(2-Cyanoethyl)(diisopropylamino)phosphanyloxymethyl]-isophthalic acid bis(N′

-monomethoxytritylhydrazide), 5-[(2-Cyanoethyl)(diisopropylamino)phosphanyloxymethyl]-isophthalic acid bis(N′

-tritylhydrazide), and 4-[(2-Cyanoethyl)(diisopropylamino)phosphanyloxymethyl]-benzoic acid N′

-monomethoxytritylhydrazide.

8. The compound of claim 1 wherein each P_Ga is mnomethoxytrityl.

9. The compound of claim 1 wherein m is 1.

10. The compound of claim 1 wherein m is 2.

11. The compound of claim 1 wherein P_r is

12. The compound of claim 1 wherein R_a and R_b are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and t-butyl.

13. The compound of claim 1 wherein R_c is 2-cyanoethyl.