Table 1.
L-Cys to L-Pen substitution in RgIA4 and their activity on human α9α10 nAChRs.
| Analog | Sequence | IC50 (nM)a | 95% CI (nM) |
|---|---|---|---|
| RgIA-5439 | G(Pen)CTDPRC(Cit) I3YQCY | >1200 | 702–2200 |
| RgIA-5408 | GC(Pen)TDPRC(Cit) I3YQCY | 1.3 | 1.03–1.6 |
| RgIA-5440 | GCCTDPR(Pen)(Cit) I3YQCY | >1000 | ND |
| RgIA-5409 | GCCTDPRC(Cit) I3YQ(Pen)Y | 24 | 11–50 |
| RgIA-5493 | G(Pen)CTDPR(Pen)(Cit) I3YQCY | > 1000 | NDb |
| RgIA-5446 | GC(Pen)TDPRC(Cit) I3YQ(Pen)Y | > 33 | ND |
| RgIA-5432c | GC(Pen)TDPRCR I3YQCY | 0.39 | 0.27–0.59 |
a
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 more than three separate oocytes. Ba2+ containing ND-96 buffer was utilized unless otherwise noted. Blue colored residues indicate change introduced into the sequence in this series of analogs. Amino acid abbreviations: Pen, L-penicillamine; Cit, L-citrulline, I3Y, 3-iodo-L-tyrosine. The C-terminus of each peptide depicted in this table is a free carboxyl group;
b
ND, not determined;