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SCIENCE CHINA Life Sciences, Volume 62 , Issue 11 : 1459-1471(2019) https://doi.org/10.1007/s11427-019-9823-1

Dynamic modifications of biomacromolecules: mechanism and chemical interventions

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  • ReceivedJul 28, 2019
  • AcceptedAug 20, 2019
  • PublishedSep 18, 2019

Abstract

Biological macromolecules (proteins, nucleic acids, polysaccharides, etc.) are the building blocks of life, which constantly undergo chemical modifications that are often reversible and spatial-temporally regulated. These dynamic properties of chemical modifications play fundamental roles in physiological processes as well as pathological changes of living systems. The Major Research Project (MRP) funded by the National Natural Science Foundation of China (NSFC)—“Dynamic modifications of biomacromolecules: mechanism and chemical interventions” aims to integrate cross-disciplinary approaches at the interface of chemistry, life sciences, medicine, mathematics, material science and information science with the following goals: (i) developing specific labeling techniques and detection methods for dynamic chemical modifications of biomacromolecules, (ii) analyzing the molecular mechanisms and functional relationships of dynamic chemical modifications of biomacromolecules, and (iii) exploring biomacromolecules and small molecule probes as potential drug targets and lead compounds.


Supplement

SUPPORTING INFORMATION

Table S1 List of research projects that have been funded by the Major Research Project at NSFC

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    The dynamic chemical modifications of biomacromolecules support the complexity of life beyond “central dogma”.

  • Figure 2

    The organization of the NSFC Major Research Plan on studying dynamic modifications of biomacromolecules.

  • Figure 3

    The computer-aided, proximal decaging (CAGE-prox) technique as a universal protein activation strategy for time-resolved study of protein functions, interactions and PTMs in living systems. A, CAGE-prox concept and workflow. B, Representative proteins of various types of enzymes activated using GAGE-prox.

  • Figure 4

    Cholesterol can covalently modify the D95 of human SMO or D99 of mouse SMO. This cholesterylation is inhibited by PTCH1 and enhanced by Shh that is also linked to cholesterol. The homozygous D99N/D99N knock-in mouse showed severe developmental defects and is embryonic lethal.

  • Figure 5

    Chemical protein synthesis of post-translationally modified proteins/probes and their representative applications for the studies of the dynamic regulation mechanisms of ubiquitin chains and ubiquitinated nucleosomes.

  • Figure 6

    Site-selective labeling of protein by the visible light initiated bioorthogonal photo-click cycloaddition.

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