. Author manuscript; available in PMC: 2022 Jul 8.

Published in final edited form as: J Med Chem. 2021 Jun 18;64(13):9271–9278. doi: 10.1021/acs.jmedchem.1c00512

Table 3.

The role of charge in position 14 of RgIA-5474 on blocking human α9α10 nAChRs.

Analog	Sequence	IC₅₀ (nM)^a	95% CI (nM)
RgIA-5474	GC(Pen)TDPRCR^I3YQC(β³hY)R	0.051	0.027–0.095
RgIA-5702	GC(Pen)TDPRCR^I3YQC(β³hY)K	0.34	0.24–0.47
RgIA-5672	GC(Pen)TDPRCR^I3YQC(β³hY)Orn	0.26	0.15–0.45
RgIA-5686	GC(Pen)TDPRCR^I3YQC(β³hY)Cit	0.40	0.27–0.601
RgIA-5687	GC(Pen)TDPRCR^I3YQC(β³hY)E	1.4	0.57–3.5

Data were collected by applying 100 μM ACh to Xenopus oocytes heterologously expressing the receptor. IC₅₀ and 95% confidence intervals (CI) are expressed as the mean ± SEM from 3–5 separate oocytes. Ca²⁺ containing ND-96 buffer was utilized. Blue colored residues indicate change introduced into the sequence in this series of analogs. Amino acid abbreviations: Pen, L-penicillamine; ^I3Y, 3-iodo-L-tyrosine; β³hY, β³-homo tyrosine; Orn, L-ornithine; Cit, L-citrulline. The C-terminus of each peptide depicted in this table is a free carboxyl group. Concentration-response curves and the Hill slope values are shown in Figure S8 and Table S2.