A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen

BMC Pharmacology

Table 1 Hit peptide names, sequences and physical properties

Name	Sequence	cyclization	Buffer Solubility (μM)	ALogP	% Inhibition of RGS4-Gα_o
YJ34	Ac-VKCTGICE-NH₂	S-S	80	-2.58	-17 ± 4 (40 μM)
1nd	YNCQGECK-NH₂	S-S	≥ 420	-2.8	2 ± 4
1ad	Ac-YNCQGECK-NH₂	S-S	123	-2.37	14 ± 6
2nd	GTCFGTCW-NH ₂	S-S	464	-0.37	19 ± 3**
2ad	Ac-GTCFGTCW-NH₂	S-S	30	0.08	10 ± 4 (10 μM)
3nd	LVCKGYCQ-NH₂	S-S	≥ 470	-0.37	12 ± 2
3ad	Ac-LVCKGYCQ-NH₂	S-S	427	0.17	10 ± 3
4nd	KVCMGGCT-NH₂	S-S	≥ 470	-2.02	4 ± 3
4ad	Ac-KVCMGGCT-NH₂	S-S	459	-2.09	9 ± 6
5nl	YWCKGLCK-NH₂	Linear	465	1.46	-1 ± 10
5al	Ac-YWCKGLCK-NH₂	Linear	460	1.66	-2 ± 4
5nd*	YWCKGLCK-NH ₂	S-S	463	0.48	80 ± 5***
5ad*	Ac-YWCKGLCK-NH ₂	S-S	464	1.04	37 ± 3***
5nm	YWCKGLCK-NH₂	S-me-S	≥ 470	0.53	3 ± 0.1 (100 μM)
6nd*	KHCYGFCY-NH ₂	S-S	Low	0.94	23 ± 15 (25 μM) *
6ad*	Ac-KHCYGFCY-NH ₂	S-S	421	1.24	27 ± 4***

Solubility in buffer was determined experimentally by HPLC. ALogP calculations are from http://www.vcclab.org, [9]. Percent inhibition values (50 μM unless otherwise stated) are from Figure 1, 2C, or 3A (mean ± S.E.M., n ≥ 3) *p < 0.05, **p < 0.01, ***p < 0.001 compared to no peptide. Peptides with significant inhibition in the FCPIA are in bold. *Peptides 5 and 6 were previously reported as peptides 7 and 14, respectively in Roof et al 2008.