Rhodamine derivatives as fluorogenic substrates for proteinases

• US 4,557,862 A
• Filed: 10/28/1983
• Issued: 12/10/1985
• Est. Priority Date: 10/28/1983
• Status: Expired due to Term

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: University Patents, Inc.
• Inventors: Mangel, Walter F., Leytus, Stephen, Melhado, L. Lee
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Draper, Garnette D.
• Application Number:
  US06/546,718
• Time in Patent Office: 774 Days
• Field of Search: 260/112 R, 260/112.5 R, 549/227, 436/800
• US Class Current: 530/331
• CPC Class Codes: C07D 493/10 Spiro-condensed systems
• CPC Class Codes: C07K 5/06078 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/06165 and Pro-amino acid; Derivatives thereof
• CPC Class Codes: C07K 5/0808 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C09B 11/24 Phthaleins containing amino groups ; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine

Abstract

The present invention relates to a new class of novel Rhodamine derivatives. These derivatives which are bisamide substitution products are nonfluorescent. Whereas the monoamide substitution products exhibit high fluorescence. Cleavage of a single specified amide bond by bond-specific proteinases will therefore convert the nonfluorescent bisamide derivative into a highly fluorescent monoamide derivative.

Claims

1. A compound of the formula:

##STR7## wherein R¹ and R², which are the same or different, are selected from the group consisting of amino acids, amino acid derivatives, blocked amino acids, blocked amino acid derivatives, and peptides.

2. A compound according to claim 1 wherein R¹ and R² are amino acids, blocked amino acids, or peptides.

3. A compound according to claim 1 wherein R¹ and R² are peptides.

4. The compounds according to claim 3 wherein R¹ and R² comprise a peptide in which the amino acid bound to the amino constituent of said formula is arginine.

5. A compound according to claim 1 wherein R¹ and R² are peptides.

6. A compound according to claim 5 wherein R¹ and R² are selected from the group consisting of dipeptides and tripeptides.

7. A compound according to claim 6 wherein at least one of the amino acid residue compounds comprising said dipeptide or tripeptide is arginine.

8. A compound of the formula:

##STR8## wherein R¹ is selected from the group consisting of amino acids, amino acid derivatives, blocked amino acids, blocked amino acid derivatives, and peptides.

9. A compound according to claim 8 wherein R¹ is selected from amino acids and peptides.

10. The compound according to claim 9 wherein R¹ is a peptide.