C-Terminal Tripeptide Mimetics

The Boehringer Ingelheim group chose a pyridone-based core structure to replace the -Glu-Glu-Ile- tripeptide of the generic SH2 domain recognition sequence [130]. From a series of more than 200 analogues, pyridones with mutually different decoration patterns were identified to result in pTyr derivatives with submicromolar affinities (e.g., 55,56) for the Lck SH2 domain [130]. 

By focusing the entire compound collection on the pTyr-pyridone scaffold, the researcher made use of a privileged structural element, since the pyridone was repeatedly utilized to induce /3 strand conformations in serine and cysteine protease inhibitors [157,158]. From this point of view, the potential of a modu- 

Exactly along this line of modification, ARI AD Pharmaceuticals succeeded in generating an Src SH2 domain antagonist containing a bicyclic core element serving as tripeptide mimic, notably AP22161 64 [161]. 

As in all cases discussed here, a tripeptide fragment was exchanged against a non-peptide module, resulting in considerably promising peptidomimetics. 

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