This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Detalhes da Produção
| Tipo | Patente |
| Grupo | Produção Técnica |
| Descrição | LU, T. K. ; FUENTE-NUNEZ, C. L. ; William Farias Porto ; FRANCO, O. L., COMPUTATIONAL PLATFORM FOR IN SILICO COMBINATORIAL SEQUENCE SPACE EXPLORATION AND ARTIFICIAL EVOLUTION OF PEPTIDES. 2018, Estados Unidos. |
| Autor | Octavio Luiz Franco |
| Ano | 2018 |
Informações Complementares
| Ano de Desenvolvimento | 2018 |
| Categoria | Produto |
| Codigo do Registro ou Patente | M0656.70434US00 |
| Data Pedido de Deposito | 20/03/2018 |
| Finalidade | Antimicrobiano |
| Informações Adicionais | Antimicrobial peptides (AMPs) represent promising alternatives to conventional 5 antibiotics, yet the translation of AMPs into the clinic is hindered by high costs of design and synthesis. We describe a computational platform for streamlining AMP design, based on a genetic algorithm that exploits a sequence space different from that of previously described AMPs. We ranked ?artificially evolved? peptides derived from Pg-AMP1, a glycine-rich peptide isolated from guava seeds, in terms of fitness function, thereby reducing cost of 10 design. This approach yielded guavanins, synthetic peptides having an unusually high proportion of arginines, and tyrosines as hydrophobic counterparts. The artificially generated peptide guavanin 2, considered an antimicrobial prototype for its potency against Pseudomonas aeruginosa, was unstructured in water and underwent a coil-to-helix transition in hydrophobic environments. NMR analysis corroborated this conformation in dodecylphosphocholine micelles, revealing an α-helical structure between residues Gln2 15 and Arg16. Guavanin 2 disrupted bacterial membranes and was bactericidal at low micromolar concentrations. In a murine abscess model, guavanin 2 reduced bacterial load significantly. This evolutionary computational approach is effective for designing peptide antibiotics |
| Informações Adicionais(en) | Antimicrobial peptides (AMPs) represent promising alternatives to conventional 5 antibiotics, yet the translation of AMPs into the clinic is hindered by high costs of design and synthesis. We describe a computational platform for streamlining AMP design, based on a genetic algorithm that exploits a sequence space different from that of previously described AMPs. We ranked ?artificially evolved? peptides derived from Pg-AMP1, a glycine-rich peptide isolated from guava seeds, in terms of fitness function, thereby reducing cost of 10 design. This approach yielded guavanins, synthetic peptides having an unusually high proportion of arginines, and tyrosines as hydrophobic counterparts. The artificially generated peptide guavanin 2, considered an antimicrobial prototype for its potency against Pseudomonas aeruginosa, was unstructured in water and underwent a coil-to-helix transition in hydrophobic environments. NMR analysis corroborated this conformation in dodecylphosphocholine micelles, revealing an α-helical structure between residues Gln2 15 and Arg16. Guavanin 2 disrupted bacterial membranes and was bactericidal at low micromolar concentrations. In a murine abscess model, guavanin 2 reduced bacterial load significantly. This evolutionary computational approach is effective for designing peptide antibiotics |
| Instituição de Deposito ou Registro | United States Patent and Trademark Office |
| Instituição Financiadora | MIT; UCB |
| Meio de Divulgação | NAO_INFORMADO |
| Número Deposito PCT | 62641513 |
| País | Estados Unidos |
| Potencial de Inovação | SIM |
| Relevância | NAO |
| Tipo de Patente | PRIVILEGIO_DE_INOVACAO_PI |
| Título | COMPUTATIONAL PLATFORM FOR IN SILICO COMBINATORIAL SEQUENCE SPACE EXPLORATION AND ARTIFICIAL EVOLUTION OF PEPTIDES |
| Título da Patente | COMPUTATIONAL PLATFORM FOR IN SILICO COMBINATORIAL SEQUENCE SPACE EXPLORATION AND ARTIFICIAL EVOLUTION OF PEPTIDES |
| Título(en) | COMPUTATIONAL PLATFORM FOR IN SILICO COMBINATORIAL SEQUENCE SPACE EXPLORATION AND ARTIFICIAL EVOLUTION OF PEPTIDES |
| Tim K Lu;Universidade Católica de Brasília;Massachusetts Institute of Technology | |
| Depósito | |
| 20032018 | |
| SIM |