SYNTHESIS OF FLUORESCENT INDICATORS FOR CYTOSOLIC CA2+

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$461,000.00
Award Year:
1988
Program:
SBIR
Phase:
Phase II
Contract:
n/a
Award Id:
4710
Agency Tracking Number:
4710
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
52 Dragon Court, Woburn, MA, 01801
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Dr Margaret E Langmuir
Principal Investigator
(617) 938-1140
Business Contact:
() -
Research Institution:
n/a
Abstract
A SERIES OF IMPROVED FLUORESCENT DYES SPECIFIC FOR COMPLEXING CA2+ WILL BE SYNTHESIZED AND EVALUATED FOR THEIR ABSORPTION AND EMISSION CHARACTERISTICS AND THEIR ABILITY TOBIND CA2+. THESE CHELATORS INCORPORATE BENZOCOUMARIN LASER DYE FLUOROPHORES, WHICH HAVE DESIRABLE HIGH-QUANTUM YIELDS AND VISIBLE WAVELENGTH ABSORPTION AND EMISSION. THE FLUOROPHORE IS ATTACHED TO AN EGTA-LIKE (ETHYLENEGLYCOL BIS [B-AMINO ETHYL ETHER N,N,N',N'-TETRAACETIC ACID]) STRUCTURE THAT IS KNOWN TO HAVE GREAT SPECIFICITY FOR CA2+ OVER MG2+ AND OTHER DIVALENT METAL IONS. THE PROPOSED CA2+ INDICATORSWILL HAVE IMPROVED OPTICAL CHARACTERISTICS OVER THOSE CURRENTLY USED (QUIN 2 AND FURA-2). THE NEW INDICATORS WILLBE CELL MEMBRANE PERMEABLE WHEN THE ACETATE GROUPS ARE ESTERIFIED, AND RECONVERTIBLE TO THE ACETATE FORM BY CYTOSOLIC ESTERASES INSIDE THE CELL. THUS THE TRAPPED CHELATOR CAN BE USED TO FOLLOW CONCENTRATION CHANGES IN INTRACELLULAR CALCIUM CONCENTRATION AS A FUNCTION OF TIME INRESPONSE TO VARIOUS PERTURBING INFLUENCES. INTRACELLULAR CALCIUM IS CURRENTLY THE SUBJECT OF WIDESPREAD INTEREST AS ASECOND MESSENGER THAT TRIGGERS AND REGULATES CELL ACTIVATION. THIS PHASE I WORK INVOLVES SYNTHESIS OF THE SUBSTITUTED BENZOCOUMARIN PORTION OF THE OVERALL STRUCTURE. IN PHASE II, THE FLUOROPHORES WILL BE LINKED TO THE EGTA- LIKE COMPLEXING AGENT. THE RESULTING SERIES OF FLUORESCENT CA2+ COMPLEXING AGENTS WILL BE EVALUATED FOR THEIR ABSORPTION AND EMISSION WAVELENGTHS AND FLUORESCENCE QUANTUM YIELD IN THE FREE AND CA2+-BOUND STATES. IN ADDITION, THEIR CA2+ COMPLEX STABILITY CONSTANTS WILL BE DETERMINED. THE MOST PROMISING INDICATORS WILL BE TESTED FOR CA2+ SPECIFICITY AND USEFULNESS INDICATORS OF INTRACELLULAR CONCENTRATION.

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government