Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China.
Center for Excellence in Post Harvest Technologies, North Carolina Agricultural and Technical State University, The North Carolina Research Campus, Kannapolis, NC 28081, USA.
Molecules. 2024 Sep 21;29(18):4483. doi: 10.3390/molecules29184483.
The zelkovamycin family is a class of cyclic octapeptides with potent antibacterial and antiviral activity. Due to their unique chemical structures and excellent bioactivity, zelkovamycins have consistently attracted the interest of synthetic chemists. However, only the total synthesis of zelkovamycin and zelkovamycin G has been reported until now. The current work presents, for the first time, the synthesis of zelkovamycin analogues, along with their anticancer activity assessment. Firstly, the corresponding chain peptide based on the amino acid sequence of zelkovamycin H was synthesized using the Fmoc solid-phase peptide strategy. This was followed by cyclization under high dilution conditions to obtain compound , and its structure was elucidated by NMR analysis. The results confirm that compound is not the natural product of zelkovamycin H. We deduced that during the synthesis of peptide , the D-Abu residue epimerized to the L-Abu form, leading to the formation of peptide , which blocked our efforts during the synthesis of zelkovamycin H. Two more analogues, and were synthesized by changing the structure of amino acid residues using the same strategy. The anticancer activity of analogues - against Huh-7 cells was evaluated in vitro; however, their IC values were >50 μM.
泽拉考霉素家族是一类具有强大抗菌和抗病毒活性的环状八肽。由于其独特的化学结构和优异的生物活性，泽拉考霉素一直吸引着合成化学家的兴趣。然而，到目前为止，只有泽拉考霉素和泽拉考霉素 G 的全合成被报道过。目前的工作首次报道了泽拉考霉素类似物的合成及其抗癌活性评估。首先，使用 Fmoc 固相肽策略合成了基于泽拉考霉素 H 氨基酸序列的相应链肽。然后，在高稀释条件下进行环化反应得到化合物 ，并通过 NMR 分析确定了其结构。结果证实化合物 不是泽拉考霉素 H 的天然产物。我们推断，在肽的合成过程中，D-Abu 残基发生差向异构化，形成 L-Abu 形式，导致肽的形成，这阻碍了我们在泽拉考霉素 H 合成过程中的努力。使用相同的策略，通过改变氨基酸残基的结构，合成了另外两种类似物 和 。体外评估了类似物 - 对 Huh-7 细胞的抗癌活性；然而，它们的 IC 值均>50 μM。
