Helical Mimetics protein surface

Complexes that feature a-helices at interfaces were studied because a-helices constitute the largest class of protein secondary structure and mediate many protein interactions [30, 51]. Helices located within the protein core are vital for the overall stability of protein tertiary structure, whereas exposed a-helices on protein surfaces constitute central bioactive regions for the recognition of numerous proteins, DNAs, and RNAs. Importantly, helix mimetics have emerged as a highly effective class of PPI inhibitors [32, 36, 44, 52-55]. 

Although biologically active helical y-peptides have not been reported so far, the striking structural similarities (polarity and helicity) between the a-helix of L-a-peptides and the (P)-2.6i4-hehx of y-peptides suggest that the 2.614-helical backbone might prove useful as a template for elaborating functional mimetics of a-helical surfaces and intervening in protein-protein interactions. 

A study by Bullock et al. revealed that roughly 60% of helical interfaces in the HIPP dataset feature helices with hot spot residues on one face of the helix (Fig. 6b, d), a third of the complexes utilize helices with hot spots on two faces (Fig. 6b, e), and roughly 10% require all three faces for interaction with the target protein partner (Fig. 6b, f). The full list of PPIs that correspond to each category is published elsewhere [67]. Overall percent occurrences of hot spot residues at the first 12 positions in interfacial helices are depicted in Fig. 6c. The results of the study indicate that helix surface mimetics may prove to be a highly effective class of synthetic... 

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