Multimeric TAT peptides are effective in vitro inhibitors of Staphylococcus saprophyticus.
Chem Biol Drug Des
; 96(6): 1348-1354, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-32562357
ABSTRACT
TAT (48-60) is a tridecapeptide from the envelope protein of HIV that was previously shown to possess cell-penetrating properties and antibacterial activity, making it a potential drug delivery agent for anticancer drugs and as antibacterial compound. Previous reports indicated that dimerization enhances the desired bioactivity of TAT; hence, we sought to synthesize multimeric TAT peptides. Herein, we describe the effects of multimerization on the antibacterial activity and secondary structure of the peptide. Terminal modifications such as N-acetylation and C-amidation were employed in the design. TATp monomer, dimer, and tetramer were synthesized using solid-phase peptide synthesis, purified by reversed-phase HPLC, and then characterized by mass spectrometry. Multimerization of the peptide did not change the secondary structure conformation. The CD analysis revealed a polyproline-II conformation for all peptide designs. Thus, this study provides a method of increasing the biological activity of the peptide by multimerization while retaining the secondary conformation of its monomeric unit. Furthermore, the bacteria Staphylococcus saprophyticus was found to be susceptible to the dimer and tetramer, with MIC50 of 12.50 µm and <1.56 µm, respectively. This suggests a structure-activity relationship whereby the antibacterial activity increases with increase in valency.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos do Gene tat do Vírus da Imunodeficiência Humana
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Staphylococcus saprophyticus
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Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
Chem Biol Drug Des
Ano de publicação:
2020
Tipo de documento:
Article