Your browser doesn't support javascript.
loading
Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides.
Ahmad Nadzirin, Izzuddin; Chor, Adam Leow Thean; Salleh, Abu Bakar; Rahman, Mohd Basyaruddin Abdul; Tejo, Bimo A.
Affiliation
  • Ahmad Nadzirin I; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia; Department of Biomedical Science, Faculty of Allied Health Science, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia. Electronic address: izzuddin_a@iium.edu.my.
  • Chor ALT; Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia. Electronic address: adamleow@upm.edu.my.
  • Salleh AB; Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia. Electronic address: abubakar@upm.edu.my.
  • Rahman MBA; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia. Electronic address: basya@upm.edu.my.
  • Tejo BA; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia. Electronic address: bimo.tejo@upm.edu.my.
Comput Biol Chem ; 92: 107487, 2021 Jun.
Article in En | MEDLINE | ID: mdl-33957477
ABSTRACT
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) is believed to be responsible for the occurrence of RA by catalyzing citrullination of proteins. The citrullinated proteins act as autoantigens by stimulating an immune response. Citrullinated α-enolase has been identified as one of the autoantigens for RA. Hence, α-enolase serves as a suitable template for design of potential peptide inhibitors against PAD4. The binding affinity of α-enolase-derived peptides and PAD4 was virtually determined using PatchDock and HADDOCK docking programs. Synthesis of the designed peptides was performed using a solid phase peptide synthesis method. The inhibitory potential of each peptide was determined experimentally by PAD4 inhibition assay and IC50 measurement. PAD4 assay data show that the N-P2 peptide is the most favourable substrate among all peptides. Further modification of N-P2 by changing the Arg residue to canavanine [P2 (Cav)] rendered it an inhibitor against PAD4 by reducing the PAD4 activity to 35 % with IC50 1.39 mM. We conclude that P2 (Cav) is a potential inhibitor against PAD4 and can serve as a starting point for the development of even more potent inhibitors.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptides / Phosphopyruvate Hydratase / Enzyme Inhibitors / Drug Discovery / Protein-Arginine Deiminase Type 4 Limits: Humans Language: En Journal: Comput Biol Chem Journal subject: BIOLOGIA / INFORMATICA MEDICA / QUIMICA Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptides / Phosphopyruvate Hydratase / Enzyme Inhibitors / Drug Discovery / Protein-Arginine Deiminase Type 4 Limits: Humans Language: En Journal: Comput Biol Chem Journal subject: BIOLOGIA / INFORMATICA MEDICA / QUIMICA Year: 2021 Document type: Article