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. Author manuscript; available in PMC: 2020 Jul 11.
Published in final edited form as: J Med Chem. 2019 Jun 27;62(13):6262–6275. doi: 10.1021/acs.jmedchem.9b00566

Figure 6.

Figure 6.

PeIA-5466 is potent and highly selective for α3β2 over α6/α3β2β3 nAChRs. Peptides based on PeIA-4769 and PeIA-5355 were synthesized with different residues in the 10th and 15th positions and a concentration–response analysis was performed for each. The IC50 values for inhibition of α3β2 and α6/α3β2β3 nAChRs for each peptide were compared to those of PeIA and the α3β2-α6/α3β2β3 selectivity ratio calculated. (A, B) PeIA-5106 and PeIA-5416 were synthesized to evaluate the effects of Nle10 and Ile15, respectively, on α3β2-α6/α3β2β3 nAChR selectivity. PeIA-5106 was 69-fold more potent than PeIA on α3β2 nAChRs, but only a minor increase (3fold) in α3β2-α6/α3β2β3 selectivity, over PeIA-4769, was found. PeIA-5416 with Ile15, was 220-fold selective for α3β2 nAChRs. An additional 70-fold enhancement of selectivity was obtained with PeIA-5466 (red curves). A minimum of 4 oocytes was used for each IC50 determination and the error bars indicate the SD; values are provided in Table 6.