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.

中文翻译：

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多聚体 TAT 肽是腐生葡萄球菌的有效体外抑制剂。

TAT (48-60) 是一种来自 HIV 包膜蛋白的十三肽，之前已证明其具有细胞穿透特性和抗菌活性，使其成为抗癌药物的潜在药物递送剂和抗菌化合物。以前的报告表明，二聚化增强了 TAT 所需的生物活性；因此，我们试图合成多聚体 TAT 肽。在此，我们描述了多聚化对肽的抗菌活性和二级结构的影响。末端修饰，如N-乙酰化和C设计中采用了酰胺化。TATp 单体、二聚体和四聚体使用固相肽合成法合成，通过反相 HPLC 纯化，然后通过质谱法表征。肽的多聚化不改变二级结构构象。CD 分析揭示了所有肽设计的聚脯氨酸-II 构象。因此，该研究提供了一种通过多聚化增加肽的生物活性同时保留其单体单元的二级构象的方法。此外，发现腐生葡萄球菌对二聚体和四聚体敏感，MIC ₅₀为 12.50 μm和 <1.56 μm， 分别。这表明了一种结构-活性关系，即抗菌活性随着化合价的增加而增加。