Office of Technology Development

Synthesis of Normal and Transformed PSA Glycopeptides for Use as a Research Tool in Prostate Cancer Diagnostics and Prognostics

SK1116

Summary of Invention

PSA is a 237-amino acid protein with a single N-glycosylation site. In contrast to PSA from normal cells that contain a dibranched carbohydrate at the glycosylation site, PSA from cancerous cells contains tri- and tetrabranched glycans. However, current assays for PSA employ antibodies against peptide epitopes only and are thus unable to distinguish between normal and “transformed” PSA. This invention consists of normal and transformed PSA glycans and glycopeptides, as well as methods for their synthesis.

Advantages

Current PSA tests have low specificity. Antibodies against specific glycoforms of PSA developed with the use of this invention could lead to improved tests for prostate cancer and allow earlier diagnosis of the disease and monitoring of its likely aggressiveness.

Area of Application

Research tool for producing antibodies against different glycoforms of PSA that can be used for diagnostics and prognostics

Stage of Development

Different glycoforms of PSA have been synthesized and are being used to immunize animals with the goal of producing selective antibodies.

Lead Inventor

Samuel Danishefsky, PhD

Patent Information

U.S. patent issued: 7, 645, 454
PCT patent application published WO 2004/060915

References

Dudkin VY, et al. (2004) J Am Chem Soc. 126(3):736-8

Contact Information

Peter Fong, PhD
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: fongp@mskcc.org

Categories

acid (A-sid)

A chemical that gives off hydrogen ions in water and forms salts by combining with certain metals. Acids have a sour taste and turn certain dyes red. Some acids made by the body, such as gastric acid, can help organs work the way they should. An example of an acid is hydrochloric acid. Acidity is measured on a scale called the pH scale. On this scale, a value of 7 is neutral, and a pH value of less than 7 to 0 shows increasing acidity.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

carbohydrate (KAR-boh-HY-drayt)

A sugar molecule. Carbohydrates can be small and simple (for example, glucose) or they can be large and complex (for example, polysaccharides such as starch, chitin or cellulose).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

diagnosis (DY-ug-NOH-sis)

The process of identifying a disease, such as cancer, from its signs and symptoms.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

peptide (PEP-tide)

A molecule that contains two or more amino acids (the molecules that join together to form proteins). Peptides that contain many amino acids are called polypeptides or proteins.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

prostate (PROS-tayt)

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

protein (PROH-teen)

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

PSA

A protein made by the prostate gland and found in the blood. PSA blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland. Also called prostate-specific antigen.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

specificity (SPEH-sih-FIH-sih-tee)

When referring to a medical test, specificity refers to the percentage of people who test negative for a specific disease among a group of people who do not have the disease. No test is 100% specific because some people who do not have the disease will test positive for it (false positive).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)