Solid-phase synthesis of DNA binding polyamides on oxime resin.
Control of the energetics and specificity of DNA binding polyamides is necessary for inhibition of protein-DNA complex formation and gene regulation studies. Typically, solid-phase methods using Boc monomers for synthesis have depended on Boc-beta-Ala-PAM resin which affords a beta-alanine-Dp tail at the C-terminus, after cleavage with N,N-dimethylaminopropylamine (Dp). To address the energetic consequences of this tail for DNA minor groove binding, we describe an alternative solid phase method employing the Kaiser oxime resin which allows the synthesis of polyamides with incrementally shortened C-terminal tails. Polyamides without Dp and having methyl amide tails rather than beta-alanine show similar affinity relative to the standard beta-Dp tail. The truncated tail diminishes the A,T base pair energetic preference of the beta-Dp tail which will allow a greater variety of DNA sequences to be targeted by hairpin polyamides.
Belitsky
J M
JM
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Nguyen
D H
DH
Wurtz
N R
NR
Dervan
Peter B
PB
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004247:DNA / Q000378:metabolism*; D016172:DNA Fingerprinting; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D003850:Deoxyribonuclease I / Q000378:metabolism; D006860:Hydrogen Bonding; D009757:Nylons / Q000138:chemical synthesis* / Q000378:metabolism; D010091:Oximes; D012117:Resins, Synthetic; D013329:Structure-Activity Relationship
D004268:DNA-Binding Proteins; D009757:Nylons; D010091:Oximes; D012117:Resins, Synthetic; D004247:DNA; D003850:Deoxyribonuclease I