Polycationic Gramicidin S Analogues with Both High Antibiotic Activity and Very Low Hemolytic Activity
| Autor: | Masahiro Kimura, Kazumasa Takanashi, Yoshiki Uchida, Makoto Tamaki, Kenta Fujinuma, Takuji Harada, Mitsuno Shindo |
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| Rok vydání: | 2012 |
| Předmět: |
Erythrocytes
Sheep Bacteria Stereochemistry medicine.drug_class Antibiotics Gramicidin Bacterial Infections General Chemistry General Medicine Gramicidin S Hemolysis Anti-Bacterial Agents chemistry.chemical_compound Residue (chemistry) Therapeutic index chemistry Drug Discovery medicine Side chain Animals Structure–activity relationship Amino acid residue |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 60:1134-1138 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | The substitution of each constituent amino acid residue of gramicidin S (GS), cyclo(-Val(1,1')-Orn(2,2')-Leu(3,3')-D-Phe(4,4')-Pro(5,5')-)(2) with Lys residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic activity and hemolytic activity of GS. Further, the substitution of D-Phe(4,4') and Pro(5,5') residues with basic amino acid residues as a Lys residue results the high antibiotic activity and the very low hemolytic activity. Thus, we have found novel positions on the scaffold of GS at D-Phe(4,4') and Pro(5,5') residues whose modification will significantly increase the therapeutic index. |
| Databáze: | OpenAIRE |
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