Antimicrobial benzodiazepine-based short cationic peptidomimetics.
J Pept Sci
; 21(6): 512-9, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-25807936
ABSTRACT
Antimicrobial peptides (AMPs) appear to be good candidates for the development of new antibiotic drugs. We describe here the synthesis of peptidomimetic compounds that are based on a benzodiazepine scaffold flanked with positively charged and hydrophobic amino acids. These compounds mimic the essential properties of cationic AMPs. The new design possesses the benzodiazepine scaffold that is comprised of two glycine amino acids and which confers flexibility and aromatic hydrophobic 'back', and two arms used for further synthesis on solid phase for incorporation of charged and hydrophobic amino acids. This approach allowed us a better understanding of the influence of these features on the antimicrobial activity and selectivity. A novel compound was discovered which has MICs of 12.5 µg/ml against Staphylococcus aureus and 25 µg/ml against Escherichia coli, similar to the well-known antimicrobial peptide MSI-78. In contrast to MSI-78, the above mentioned compound has lower lytic effect against mammalian red blood cells. These peptidomimetic compounds will pave the way for future design of potent synthetic mimics of AMPs for therapeutic and biomedical applications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Staphylococcus aureus
/
Benzodiazepinas
/
Cationes
/
Escherichia coli
/
Peptidomiméticos
/
Antiinfecciosos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Pept Sci
Asunto de la revista:
BIOQUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Israel