Isostable proteins

Ichthyocoll is an isostable protein, which — apart from a different position of the isoelectric point — is in the main similar to gelatin in properties. Here as in the case of gelatin a simple behaviour is only present at temperatures (for example 37°) at which no gelation processes, whether slow or rapid, occur. 

Lamos and colleagues reported the modification of cyclophilin A (CypA) by binding immunosuppressive cyclosporin A with a benzophenone-Dj j and a biotin moiety (compound 89, Fig. 11a) [91]. As a proof of principle, they used a 1 1 mixture of this TIP and its nondeuterated isoster for the selective PAL and pulldown of CypA among three other proteins. Subsequent tryptic digestion of the elutes and LC-MS/MS analysis allowed the identification of 11 CypA characteristic peptides, two of which were modified with the probe, as evidenced from the double, 11 Da separated, peaks in the mass spectra. The large 11-Da mass difference allowed easy visual recognition of labeled peptides in the mass spectra, which makes this a powerful method for determination of the modification site after PAL however, application in more complex systems still remains to be done. 

In another application, STED microscopy also revealed the ring-like structure of the protein hruchpilot at synaptic active zones in the drosophila neuromuscular junction [90], Further studies included the visualization of the spatial distribution of the SNARE protein syntaxin [91], the nuclear protein SC35 [85], and the nicotinic acetylcholine receptor [92]. IsoSTED microscopy resolved the tube-like 3D-distribution of the TOM20 protein complex in the mitochondria in a mammalian cell [87]. 

Numerous nucleoside antibiotics are known. For instance, 9-(p-i)-arabinofuranosyl)adenine 48 possesses antiviral and antitumor activity, puromycin 49 is an inhibitor of protein biosynthesis in bacteria and mammalian cells, tubercidin 50 (as example of a purine isoster, isolated from Streptomyces) possesses anticancer activity. 

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