Synthesis of fluorescent microgonotropens (FMGTs) and their interactions with dsDNA.
A new class of microgonotropen compounds (FIMGTs), which fluoresce upon binding to dsDNA, is introduced. The FMGTs consist of a minor groove binding moiety based upon Hoescht 33258 covalently attached to a polyamine chain capable of interacting with the phosphodiester backbone of dsDNA. The interactions of FMGTs with dsDNA were investigated by fluorescence and UV spectroscopy. Several different dsDNA oligomers were studied to determine the effect of binding site sequence on stoichiometric and binding affinity. The FMGTs were found to bind a dsDNA oligomer that contained the sequence 5'-AATTT-3' with FMGT:dsDNA stoichiometrics equal to 2:1 or 3:1. Hoechst 33258 bound the same dsDNA oligomer with a 1:1 stoichiometry. The second and third order equilibrium constants for complexation were determined to be Log(K1K2) = 17.9 M(-2) and Log(K1K2K3) = 26.1 M(-3), respectively, for two of strongest binding FMGTs. From thermal melting experiments deltaTm for Hoechst 33258 was determined to be 10 degrees C while the deltaTm values for FMGTs ranged from 20-26 degrees C indicating the greater stability of the latter.
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Department of Chemistry, University of California at Santa Barbara, 93106, USA.
Bruice
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D006690:Bisbenzimidazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004214:Distamycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry* / Q000378:metabolism; D013057:Spectrum Analysis; D013696:Temperature
D004214:Distamycins; D005456:Fluorescent Dyes; D011073:Polyamines; D004247:DNA; D006690:Bisbenzimidazole