From transcription factors to designed sequence-specific DNA-binding peptides

Abstract

Transcription factors are DNA-binding proteins responsible for initiating the transcription of particular genes upon interacting with specific DNA sequences located at their promoter or enhancer regions. The DNA recognition process, which is extremely selective, is mediated by non-covalent interactions between appropriately arranged structural motifs of the protein and exposed surfaces of the DNA bases and backbone. The great variability in DNA recognition by transcription factors has hampered the characterization of an amino acid-base step recognition code, making it very difficult to design non-natural peptides that can mimic the DNA-binding properties of these naturally occurring counterparts. However, in recent years, several transcription factor-based miniature proteins capable of tight interaction with specific DNA sites have been successfully constructed, most of them using bottom-up synthetic approaches.

Single‐Molecule Experiments in Synthetic Biology: An Approach to the Affinity Ranking of DNA‐Binding Peptides

“…In summary, there is evidence that the native sequence and the mutants R193A and H198A specifically recognize the PhoB target sequence. As it was doubted recently that short peptide sequences with only one a helix are capable of specific DNA binding, [1] our results are quite remarkable given that the 20-residue peptides represent a rather small epitope from the binding domain of the protein.…”

“…In this way, cell growth, differentiation, and development are regulated. The possibility to influence and control cell metabolism through modified synthetic transcription factors [1][2][3][4] offers fascinating prospects for molecular cell biology in the framework of biomimetics and synthetic biology. [5,6] The design and synthesis of biologically active artificial enzymes and new protein-based materials can be investigated by the combination of bioorganic bottom-up synthesis and single-molecule affinity nanotechnology.…”

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

“…Progress in cancer research over the last 25 years has led to the inescapable conclusion that neoplasia is a malady of genes [1][2][3][4][5]. A large number of malignancies that do not respond to chemotherapy underline the need to develop safe and effective antitumour drugs.…”

Effects of supercoiling on the sequence-specific photo-modification of DNA by a vanadium(V)-peroxo complex

“…Taking advantage of the considerable progress made in identifying the crucial molecular determinants for site-and sequence-specific interactions with DNA [2][3][4][5][6][7][8], the treatment of diseases based on modulation of specific genes is becoming a realizable goal in molecular medicine [9][10][11]. Following the successful development of cisplatin as an antitumor drug [12], many metal-based complexes capable of DNA and RNA scissions have been designed as specific structural probes for both the primary (sequence) and secondary (conformation) structures of nucleic acids [13][14][15][16][17].…”