Design of Sequence‐Specific DNA‐Binding Ligands

Abstract

The cover picture shows two molecular orbitals of square-planar [Rh(acac)(CO),] complexes interacting in a dimer or a chain (produced with the Cerius2 package). The metal d,, orbital (bottom) acts as a donor toward the carbonyl n& orbital, thanks to the mixing of the latter with the metal d,, orbital in the molecular orbital shown in the top half of the picture. Interactions of this type operate in chains of mixed-ligand square-planar complexes when two of the ligands have stronger nacidic character than the other two and account for the relative rotation of two successive monomers in a chain and for the zigzag shape of the metal backbone. A detailed discussion of how the naturc of the ligands affects the strength of the metal -metal interactions in such chains, based on molecular orbital arguments and structural database correlations, is presented by G. Aullon and S. Alvarez on p. 655ff.

Double duplex invasion by peptide nucleic acid: A general principle for sequence-specific targeting of double-stranded DNA

“…Yield 1.8 g (80%). 1 PNA oligomer synthesis. PNA oligomers were prepared on a MBHA resin by standard procedures (15) and were purified by HPLC.…”

“…eneral principles for design of synthetic reagents that sequence-specifically recognize and bind desired targets in double-stranded DNA have been long-sought goals in chemistry and molecular biology (1)(2)(3). Three approaches, triplex-forming oligonucleotides (2-4), helix-invading peptide nucleic acids (PNAs) (5,6), and side-by-side minor groove binders (7,8), have accomplished impressive progress during the past 10 years, but unresolved limitations on sequence choice and͞or target length and specificity still exist for all approaches.…”

Advances in DNA-Ligands with Groove Binding, Intercalating and/or Alkylating Activity: Chemistry, DNA-Binding and Biology

“…Peptide nucleic acids (PNAs) are recently described as DNA mimetics, in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine units [15][16][17]73]. A structural comparison of a peptide chain and a PNA molecule interacting with a normal DNA strand is given in Fig.…”

“…The synthesis and testing of analogues of the natural occurring oligopyrrole carboxamides is a subject of the [4,7,25,26,27], hybrid molecules [28], peptide nucleic acids [15,16] and topoisomerase I-inhibitors [29]. current active research.…”

“…The general chemical structure is represented by 7. In this context of sequence reading molecules some results about peptide nucleic acids 8 and related compounds (see for example nucleobase linked derivative 6) [15][16][17] are also presented. In summary, these molecule series are on the one hand of general interest for anticancer/antisense therapy, and on the other hand they represent a useful tool in academic research for molecular biological operations in the context of gene manipulation or gene silencing processes [8,18].…”