Table 3 Summary of binding affinities and in vitro activity of cP4_4 and its variants where the fluoroacetimidoyl ornithine (FAO) warhead was replaced by arginine (Arg4), citrulline (Cit4), acetimidoyl ornithine (Me4) or chloroacetimidoyl ornithine (Cl4)

From: Discovering covalent cyclic peptide inhibitors of peptidyl arginine deiminase 4 (PADI4) using mRNA-display with a genetically encoded electrophilic warhead

 

SPR

COLDERS

 

Ki (µM)

kinact (min-1)

kinact/Ki (M-1 min-1)

KD (µM)

IC50 (µM) T = 0 h

IC50 (µM) T = 1 h

Arg4

–

–

–

2.0 ± 0.2

>100

 

Cit4

–

–

–

>10

>100

 

Me4

–

–

–

1.7 ± 0.4

>20

 

Cl4

4.0 ± 0.2

0.28 ± 0.02

70,000

–

8.2 ± 0.8

0.066 ± 0.009

cP4_4

0.12 ± 0.01

0.11 ± 0.003

909,000

–

4.4 ± 0.07

0.070 ± 0.004

  1. Surface plasmon resonance (SPR) data shows mean ± SEM of three independent replicates. COLDER data shows mean ± SEM of at least two independent replicates.
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