The title bifunctional (polyfunctional) organic reagents will be synthesized, and tested as cross-linkers of hemoglobin and oxyhemoglobin. Previously, two examples of the title compounds were characterized in our laboratory. The general approach that entails the regiospecific addition of 1,n-alkanedisulfonyl chloride to allyl chloride in a key step will be utilized. We shall extend the synthetic approach to include """"""""ether"""""""" and """"""""sulfone"""""""" functions in the """"""""linkers"""""""" of reactive sites of the reagent. Hydrophilic functional groups in the """"""""linkers"""""""" of the reactive sites, N,N- dialkyl 2-sulfonyl-1-amino-2-propenes, are expected to lead to significant levels of solubility in an aqueous environment. In our initial efforts, we shall synthesize two bifunctional organic reagents derived from a 1,5- disubstituted pentane: 1,5-bis-(N,N-diisopropyl 2-sulfonyl-1 -amino-2- propene)-3-oxapentane and 1,5-bis-(N,N-diisopropyl 2-sulfonyl-1-amino-2 propene)-3-thiapentene 3,3-dioxide. The design of this series of reagents allows us to vary the chemical reactivity and the length of the """"""""linkers"""""""" in a systematic way. Chemical reactivities and selectivities of the organic cross-linking reagents will be assessed through an investigation of reactions (product studies and rate data) of the reagents with models of proteins and nucleic acids, hydrochlorides of amino acid esters and nucleotides (and/or their bases), respectively. Upon completion of the proposed studies, the effectiveness of the title reagents as cross linkers of hemoglobin and oxyhemoglobin will have been determined as a function of """"""""linker"""""""" in length, solubility, and chemical reactivity. The selectivities and reactivities of the cross-linking reagents toward hemoglobin and oxyhemoglobin will be determined by isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis. While this proposal focuses primarily on the development of crosslinking reagents for hemoglobin and oxyhemoglobin, the title compounds will be examined as modifiers of nucleic acids and histones.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Southern University A&M Col Baton Rouge
Department
Type
DUNS #
City
Baton Rouge
State
LA
Country
United States
Zip Code
70813
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