PRODUCTION OF A HORMONE RECEPTOR COMPETITIVE ANTAGONIST

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$50,000.00
Award Year:
1988
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Award Id:
7939
Agency Tracking Number:
7939
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
1 Mountain Rd, Framingham, MA, 01701
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
() -
Business Contact:
() -
Research Institute:
n/a
Abstract
RECENT RESEARCH IN REPRODUCTIVE ENDOCRINOLOGY HAS DEMONSTRATED THE IMPORTANCE OF FOLLICLE STIMULATING HORMONE (FSH) IN THE REGULATION OF GAMETOGENESIS AND GONADAL STEROIDPRODUCTION. IT HAS BEEN SHOWN THAT N-LINKED OLIGOSACCHARIDES, ATTACHED TO ASPARAGINE RESIDUES AT SPECIFIC SITES ALONG THE MOLECULE, ARE ESSENTIAL FOR POST-RECEPTOR TARGET CELL ACTIVATION BUT NOT RECEPTOR BINDING. THESE SUGARS ALSO PLAY A ROLE IN DETERMINING THE HALF-LIFE OF THE MOLECULE IN CIRCULATION. WE PLAN TO USE THE TECHNIQUE OF SITE-DIRECTED MUTAGENESIS TO PRODUCE A RECOMBINANT HUMAN FSH MOLECULE THAT WILL HAVE ONE OR MORE OFTHE ASPARAGINE RESIDUES REPLACED WITH A SIMILARLY CHARGED AMINO ACID TO "ERASE" THE SITE OF N-LINKED SUGAR ATTACHMENT.PRELIMINARY STUDIES HAVE SHOWN THAT REMOVAL OF SUGARS FROM THE ALPHA CHAIN SEVERELY DECREASE BIOLOGIC ACTIVITY. REMOVAL OF THESE SUGAR RESIDUES, BY MUTAGENESIS, WILL PRODUCE A LONG ACTING COMPETITIVE ANTAGONIST OF FSH, WHICH, WHEN ADMINISTERED TO HUMANS, WOULD BE EXPECTED TO RESULT IN AN ANOVULATORY STATE OR AZOSPERMIA. A MUTAGENIZED, RECOMBINANT HORMONE MAY BE PRODUCED IN LARGE AMOUNTS, WITH EACH BATCH EXHIBITING UNIFORM BIOCHEMICAL AND BIOLOGICAL PROPERTIES. THEREFORE, THIS PRODUCT WOULD BE AN EXCELLENT CHOICE AS A REVERSIBLE CONTRACEPTIVE IN MEN AND WOMEN.

* information listed above is at the time of submission.

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