Crystallization peptide-mimetics

Inhibition of the zinc peptidase thermolysin has been the target of peptide mimetic effort by Bartlett and co-workers at the University of California at Berkeley. The researchers began by investigating the X-ray crystal structure of this enzyme with the known peptidic inhibitor Cbz-GlyP-Leu-Leu (Gly " represents the phosphonic acid analogue of glycine). This inhibitor has a fCj of 9 nM against the enzyme. The authors reasoned that the inhibitor could be confer-... 

When detailed three-dimensional X-ray crystal structure information is available for the targeted receptor, additional computational tools can be employed as part of the peptide mimetic design effort. In these situations it is... 

A common feature of nearly all X-ray crystal complexes between HIVPR and peptide-derived peptidomimetic inhibitors (PPIs) is the presence of a tetracoordinated structural water molecule tightly bound between the inhibitor molecule and the flexible beta strands or flaps of the HIVPR dimer. This ubiquitous water molecule accepts two hydrogen bonds from backbone amide bonds of flap residues IleSO and IleSO and donates two hydrogen bonds to suitable acceptors, typically carbonyl groups, which flank the transition state isostere of the peptide mimetic inhibitor (Fig. 3a) [31]. Potent... 

Erythropoietin is a glycoprotein hormone that regulates the proliferation, differentiation, and maturation of erythroid cells. The EPO receptor is a member of the class 1 cytokine receptor superfamily. The crystal structure of an EPO-mimetic peptide and the extracellular portion of the... 

Fig. 2.1 Crystal structure of a complex of the extracellular domain of the human erythropoietin receptor (EBP) and an agonist peptide, the EPO-mimetic peptide 1 (EMPl).

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