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Science 25 April 1986:
Vol. 232. no. 4749, pp. 464 - 471
DOI: 10.1126/science.2421408
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Articles

Science, Vol 232, Issue 4749, 464-471
Copyright © 1986 by American Association for the Advancement of Science

articles

Design of sequence-specific DNA-binding molecules

PB Dervan

Base sequence information can be stored in the local structure of right-handed double-helical DNA (B-DNA). The question arises as to whether a set of rules for the three-dimensional readout of the B-DNA helix can be developed. This would allow the design of synthetic molecules that bind DNA of any specific sequence and site size. There are four stages of development for each new synthetic sequence-specific DNA-binding molecule: design, synthesis, testing for sequence specificity, and reevaluation of the design. This approach has produced bis(distamycin)fumaramide, a synthetic, crescent-shaped oligopeptide that binds nine contiguous adenine-thymine base pairs in the minor groove of double-helical DNA.


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