# US 5,702,908 A · Interruption of binding of MDM2 and p53 protein and therapeutic application thereof

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- Number: US 5,702,908 A
- Document ID: US5702908A
- Status: Granted
- Kind: A
- Application number: 08/277,660
- Filed: 1994-07-20
- Granted: 1997-12-30
- Earliest claimed: 1994-07-20
- Assignees: University of Dundee
- Inventors: Steven Michael Picksley; David Philip Lane
- Web page: https://patentgrep.com/patent/US5702908A

## CPC

- C07K 14/82: Translation products from oncogenes
- C07K 14/4746: {p53}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A method of identifying a compound which interferes with the binding of MDM2 to human p53 has been determined. This method comprises forming a mixture between MDM2 and a fragment of human p53 consisting of 6 to 28 amino acids comprising TFSDLW (SEQ ID NO:2), adding a test compound to the mixture and determining the quantity of protein bound to the other before and after adding the compound. A compound which decreases the amount of binding of the two proteins to each other is a compound which interferes with the binding of MDM2 to human p53.

## Claims

### Claim 1

A method of identifying a compound which interferes with the binding of MDM2 to human p53, said method comprising the steps of:
forming a mixture by combining a labeled first protein with a second protein, wherein one of the first protein or the second protein is MDM2 and the other is a fragment of human p53 consisting of 6 to 28 amino acids comprising the amino acid sequence TFSDLW (SEQ ID NO:2) or a peptide analogue thereof;
adding a test compound to the mixture; and
determining the quantity of the first protein which is bound to the second protein before and after said adding step, wherein a decrease in the quantity of the first protein which is bound to the second protein after the adding step indicates that the test compound is a compound which interferes with the binding of MDM2 to human p53.

### Claim 2 (depends on 1)

The method of claim 1 wherein the fragment of human p53 consists of 12 to 28 amino acids comprising the amino acid sequence TFSDLW (SEQ ID NO:2).

### Claim 3 (depends on 1)

The method of claim 1 wherein said method is performed as a high throughput screen.

### Claim 4 (depends on 1)

The method of claim 1 wherein the test compound is a peptide from a synthetic combinatorial peptide library.

### Claim 5 (depends on 1)

The method of claim 1 wherein said MDM2 is human MDM2.