69983-47-7Relevant articles and documents
Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent
Singh, Palwinder,Kaur, Sukhmeet,Kaur, Jagroop,Singh, Gurjit,Bhatti, Rajbir
, p. 3920 - 3934 (2016/05/24)
Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 ± 1.10 × 104 M-1 and ΔG of -100.3 kJ mol-1 in comparison to a Ka 0.41 × 103 ± 0.09 M-1 and ΔG of -19.2 ± 0.06 kJ mol-1 for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg-1 dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.
