A microgonotropen branched decaaza decabutylamine and its DNA and DNA/transcription factor interactions.
The central pyrrole of a site-selective DNA minor groove binding tripyrrole peptide 1 has been attached to a branched decaaza decabutylamine via a -(CH-2)3-NHCO-(CH2)-3 linker to provide the decaaza-microgonotropen (8). The decaaza decabutylamine moiety of 8 was designed to have a much greater affinity to the phosphodiester linkages of the backbone of DNA. Employing Hoechst 33258 (Ht) as a fluorescent titrant, the equilibrium constants for the binding for of 8 to the hexadecameric duplex d(GGCGCA3T3GGCGG)/d(CCGCCA3T3GCGCC) and to calf thymus DNA were determined. The log of the product of equilibrium constants (log Kl1Kl2) for 1:1 and 1:2 complexes formation at A3T3 is 17 (35 degrees C). Results of studies of the inhibition of the binding of several proteins to target DNA are discussed. Binding of the E2F1 transcription factor to its DNA target is 50% inhibited at approximately 2 nM concentration of 8.
Bruice
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TC
Department of Chemistry, University of California, Santa Barbara 93106, USA.
Sengupta
D
D
Blaskó
A
A
Chiang
S Y
SY
Beerman
T A
TA
D000818:Animals; D006690:Bisbenzimidazole / Q000737:chemistry; D002082:Butylamines / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D018797:Cell Cycle Proteins; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004214:Distamycins / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004591:Electrophoresis, Polyacrylamide Gel; D033862:Iron-Binding Proteins; D007700:Kinetics; D015345:Oligonucleotide Probes; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D016385:TATA Box; D035181:TATA-Box Binding Protein; D013950:Thymus Gland / Q000378:metabolism; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D033863:Transferrin-Binding Proteins; D016335:Zinc Fingers
D002082:Butylamines; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004214:Distamycins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D033862:Iron-Binding Proteins; D015345:Oligonucleotide Probes; D011758:Pyrroles; D056465:Retinoblastoma-Binding Protein 1; D035181:TATA-Box Binding Protein; D050680:Transcription Factor DP1; D014157:Transcription Factors; D033863:Transferrin-Binding Proteins; C030000:stallimycin; D004247:DNA; D006690:Bisbenzimidazole