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High - Throughput Generation of Small Antibacterial Peptides With Improved Activity
Oleh:
Hilpert, Kai
;
Volkmer-Engert, Rudolf
;
Walter, Tess
;
Hancock, Robert E.W.
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 8 (Agu. 2005)
,
page 1008-1012.
Topik:
antibacterial
;
generation
;
antibacterial peptides
;
activity
Ketersediaan
Perpustakaan Pusat (Semanggi)
Nomor Panggil:
NN9.4
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
Cationic antimicrobial peptides are able to kill a broad variety of gram negative and gram positive bacteria and thus are good candidates for a new generation of antibiotics to treat multidrug resistant bacteria. Here we describe a high throughput method to screen large numbers of peptides for improved antimicrobial activity. The method relies on peptide synthesis on a cellulose support and a pseudomonas aeruginosa strain that constitutively expresses bacterial luciferase. A complete substitution library of 12-amino acid peptides based on alinearized variant (RLARIVVIRVARNH2) of the bovine peptide bactenecin was screened and used to determine which substitutions at each position of the peptide chain improved activity. By combining the most favorable substitutions, we designed optimized 12-mer peptides showing broad spectrum activities with minimal inhibitory concentrations (MIC) as low as 0,5 ug/ml against escherichia coli. Similarly, we generated an 8-mer substituted peptide that showed broad spectrum activity, with an MIC of 2 ug / ml, against E. coli and staphylococcus aureus.
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