Lifeline for aging cells

Scientists have found a small molecule that can be used to extend the lifespan of mammalian cells. The research reported in the July issue of Nature Chemical Biology showed that the synthetic organic molecule CGK733 blocks the machinery that senses DNA damage.

All cells face an inevitable death as they age. On this path, cells may become senescent, where they stay alive but stop dividing. In looking for chemicals that can help cells beat senescence, Tae Kook Kim and colleagues screened a library of synthetic compounds for those that could stimulate growth and other visual signs they could help cells overcome this state. They found that CGK733 could extend the lifetime of cultured cells by about 20 doublings and could actually rescue cells that were already senescent. To do this, CGK733 blocks the checkpoint involved in sensing and slowing down cells in response to DNA damage.

By blocking a natural event that leads to senescence, CGK733 confers life-saving and life-extending properties on mammalian cells.

Tumor homing device

Scientists have developed a tool that can be used for diagnostic imaging and targeted therapy of tumors. The research, reported in the July issue of Nature Chemical Biology, shows that a small protein can bind to the surface of leukemia cells and home in on the tumors. The researchers also suggest that the protein could potentially help to deliver drugs to treat the tumor.

The migration or metastasis of tumor cells requires adhesive connections between receptors on the surface of cells and components of the matrix that makes up the extracellular environment. Kit Lam and colleagues used a unique strategy to find peptides based on sequences involved in these connections. One of the lead compounds, 2A could bind to the surface of leukemia cells that express a specific cell surface receptor involved in migration, integrin alpha4beta1. 2A could also mark tumor cells within mice, but ignored normal surrounding cells. The remarkable specificity of 2A for tumor cells that express alpha4beta1 makes it useful for imaging tumors.

2A was designed to be highly stable and so can also be used to deliver a toxic compound to tumors.

Small molecule-based reversible reprogramming of cellular lifespan

Jaejoon Won, Mina Kim, Nuri Kim, Jin Hee Ahn, Woo Gil Lee, Sung Soo Kim, Ki-Young Chang, Yong-Weon Yi and Tae Kook Kim

Published online: 11 June 2006 | doi 10.1038/nchembio800

Abstract | Full text | PDF | Supplementary information

Combinatorial chemistry identifies high-affinity peptidomimetics against α4β1 integrin for in vivo tumor imaging

Li Peng, Ruiwu Liu, Jan Marik, Xiaobing Wang, Yoshikazu Takada and Kit S Lam

Published online: 11 June 2006 | doi 10.1038/nchembio798

Abstract | Full text | PDF | Supplementary information