Institut de Recerca Biomèdica, Baldiri Reixach, Barcelona, Spain.
Bioorg Med Chem. 2010 Dec 1;18(23):8350-5. doi: 10.1016/j.bmc.2010.09.066. Epub 2010 Oct 7.
Specific proteolytic processing of inactive precursors is an exquisite cellular mechanism that triggers the activation of numerous physiologic peptides and proteins. This process ensures the generation of biologically active peptides, such as many neuropeptides and peptide hormones, in the appropriate cellular compartments at the right time, and its failure leads to several pathological conditions. Identification of the proteases involved in this limited proteolysis is, therefore, an essential step for the subsequent establishment of new therapeutic targets. As a first effort along this line, we synthesized eight new dipeptidyl phosphonate activity-based probes and used them to explore the soluble proteome from mouse brain and pituitary gland for substrate-based protease identification both by in-gel analysis and mass spectrometry.
特定的无活性前体蛋白的蛋白水解加工是一种精细的细胞机制，它触发了许多生理肽和蛋白质的激活。这个过程确保了生物活性肽的产生，如许多神经肽和肽类激素，在适当的细胞隔室中在正确的时间，其失败导致几种病理状况。因此，鉴定参与这种有限水解的蛋白酶是随后建立新的治疗靶点的关键步骤。作为沿着这条线的初步努力，我们合成了八个新的二肽磷酸基活性探针，并将其用于通过凝胶内分析和质谱法来探索来自小鼠脑和垂体的可溶性蛋白质组以进行基于底物的蛋白酶鉴定。
