Mitomycin-Oligonucleotides for Vascular Therapy

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$74,850.00
Award Year:
1994
Program:
SBIR
Phase:
Phase I
Contract:
1 R43 HL51778-1,
Award Id:
25150
Agency Tracking Number:
25150
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
7000 Fannin, Ste 1920, Houston, TX, 77030
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Timothy Kogan
(713) 796-8822
Business Contact:
() -
Research Institution:
n/a
Abstract
The research objective is synthesis of a conjugate of mitomycin C to an antisense phosphorothio-ate nucleotide targeted to proliferating smooth muscle cells responsible for arterial occlusion. This wouldprovide a novel approach to the prevention of restenosis, for which there is currently no effectivemedicinal intervention available. Mitomycins will be derivatized with a linking group to permit covalentattachment to the 5' end of end of an antisense oligonucleotide, either while attached to the solidsupport, or after cleavage of the oligonucleotide from the solid support. Compounds will be assayed ina cell culture assay to evaluate the effectiveness of such agents compared to either of the componentsindividually or co-administered,to determine if synergistic activity against cell proliferation is achieved.In principle, we envisage the antisense oligonucleotide hybridizing with RNA in a smooth muscle cell andpermitting the attached mitomycin C to covalently modify an adjacent guanine base, thereby preventingtranscription of the target gene, and preventing cell cycling. Such permanent modification may beanticipated to be more effective than oligonucleotide hybridization alone, while operating at a sub-toxicdose of mitomycin C. The site of the mitomycin-oligonucleotide conjugate bonding to RNA in vitro forpromising drug candidates will be verified by melting point (Tm) measurements prior to drug activationand by the reverse transcriptase assay after drug activation.

* information listed above is at the time of submission.

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