4.6 Article

Selective homodimerization of unprotected peptides using hybrid hydroxydimethylsilane derivatives

期刊

RSC ADVANCES
卷 6, 期 39, 页码 32905-32914

出版社

ROYAL SOC CHEMISTRY
DOI: 10.1039/c6ra06075g

关键词

-

资金

  1. ITMO cancer
  2. Region Languedoc Roussillon through 'Chercheur d'avenir'

向作者/读者索取更多资源

We developed a simple and straightforward way to dimerize unprotected peptide sequences that relies on a chemoselective condensation of hybrid peptides bearing a hydroxydimethylsilyl group at a chosen position (either C-ter, N-ter or side-chain linked) to generate siloxane bonds upon freeze-drying. Interestingly, the siloxane bond sensitivity to hydrolysis is strongly pH-dependent. Thus, we investigated the stability of siloxane dimers in different experimental conditions. For that purpose, Si-29, C-13 and H-1 NMR spectra were recorded to accurately quantify the ratio of dimer/monomer. More interestingly, we showed that H-1 resonances of the methylene and methyl groups connected to the Si can be used as sensitive probes to monitor siloxane hydrolysis and to determine the half-lives of the dimers. Importantly, we showed that the dimers were rather stable at pH 7.4 (t(1/2) approximate to 400 h) and we applied the dimerization strategy to bioactive sequences. Once optimized, three dimers of the growth hormone releasing hexapeptide (GHRP-6) were prepared. Interestingly, their pharmacological evaluation revealed that the activity of the dimeric ligands could be switched from agonist to inverse agonist depending on the position of dimerization.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据