A review on the types of amino acid at ultimate, penultimate and antepenultimate position in some dipeptidyl-peptidase IV inhibitory peptides based on molecular docking analysis

Abstract

This review focused on assessing the type of amino acids at terminal positions of previously reported DPPIV inhibitory peptides to predict the key feature of sequences that specifically target DPPIV. Thorough understanding on side chain property of reactive amino acids and its contribution on DPPIV recognition and binding was acquired through structure-activity relationship and molecular docking analysis. Overall, N-terminals dominant by Leu, Pro, Ile, Phe, Ala, Tyr and/or Gly, whereas C-terminals dominant by Arg, Phe, Met, Ala, Val, Pro, Gln, Ile, Glu, Leu and/or Lys depending on the peptide length and terminal positions where these reactive residues hydrophobically interacted with the catalytic (Ser630) or substrate-binding (Tyr629, Tyr547, Tyr666 and Phe357) hotspots of DPPIV. Molecular docking prediction also suggested the presence of secondary hotspots (Arg125, His126, Gly355, Pro359, Ile405, Asp545, Val546, Cys551, Cys552, Gln553, Trp627, Tyr662, Ala707, Asp709, Glu738, Asp739, Gly741, Ile742 and Tyr752) to support peptide binding. In conclusion, outcome of the current review could inspire the design of potent DPPIV inhibitory peptides where the preference for hydrophobic and aliphatic reactive amino acids could be translated into candidate DPPIV-targeting sequences given their ability to engage with DPPIV hotspots.

Keywords

• Anti-diabetes
• Bioactive peptide
• DPPIV hotspots
• DPPIV inhibitor
• Molecular docking
• Structure-activity relationship