De novo design of peptides with L-alpha-nucleobase amino acids and their binding properties to the P22 boxB RNA and its mutants.
A method to design novel molecules that specifically recognize a structured RNA would be a promising tool for the development of drugs or probes targeting RNA. In this study, the de novo design of the alpha-helical peptides having L-alpha-amino acids with nucleobases (nucleobase amino acids, NBAs) was carried out. Binding affinities of the peptides for a hairpin RNA derived from P22 phage were dependent on the types and positions of the NBA units they have. Some NBA peptides bound to the wild-type RNA or its mutant with high affinity and high specificity compared with the native P22 N peptide. These results indicate that the NBA units on the peptides interact with the RNA bases in a specific manner. It is demonstrated that the de novo design of peptides with the NBA units is an effective way to construct novel RNA-binding molecules.
Miyanishi
Hideo
H
Department of Bioengineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
Takahashi
Tsuyoshi
T
Mihara
Hisakazu
H
D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D015195:Drug Design; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics*; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D009711:Nucleotides; D010455:Peptides; D016601:RNA-Binding Proteins; D012313:RNA