H24_分子情報科学_6月29日.doc

ケミカルバイオロジーに関する学術論文を１報選び、概要およびその論文に対する自分の意見を述べよ。
Select an academic paper concerned with Chemical Biology. Summarize the contents and describe your opinion about the paper.

Interest in cleavable linkers is growing due to the rapid development and expansion of chemical biology. The chemical constrains imposed by the biological conditions cause significant challenges for organic chemists.

In the introduction part, Leriche et al. introduced the background and the prospect of cleavable linkers in chemical biology. In this review, they defined a linker as a molecule with two functional heads joined together through a cleavable bond. The functional heads served to interact with or to manipulate the biological target; they could be reactive groups for protein crosslinking, ligation or for click chemistry; fluorescent probes for diagnostic tools, proteomic analysis or cell imaging; tags for MS analysis or purification; targeting molecules for functional proteomics or activity based probe profiling (ABPP). The flexibility in the design of the cleavable linkers had led to their application in many different biological disciplines including drug development, proteomics, imaging and DNA sequencing. And they introduced when the linkers were used in different fields, drug development, proteomics, imaging, and DNA sequencing, what were the demands the linkers should meet.

After the introduction, they outlined seven different classes of cleavable linker used in chemical biology. They were
1) Enzymatically cleavable linkers
Chemo-selectivity and biocompatibility, however specific peptide sequence required
2) Nucleophile/base sensitive linkers
Release proteins from a solid support efficiently, however, a medium with a basic pH required
3) Reduction sensitive linkers
Chemically stable in physiological conditions, however, the compatibility of sodium dithionite with disulfide bridges has not yet been demonstrated
4) Photocleavable linkers
Widely used in chemical biology and many different photo labile structures permit efficient cleavage, however, the wavelength of light had limitation
5) Electrophile/acid sensitive linkers
Very versatile, however, For protein purification, high pH could led to non specific cleavage and protein denaturation
6) Oxidation sensitive linkers
Many application in structural biology

According to this paper, I knew about a lot of basic things about chemical cleavable linkers. The interest in cleavable linkers is growing due to the rapid development and expansion of chemical biology. It was very interesting. This review also introduced many kinds of linkers. And the words used in this literature were easier for me to understand the content.