Abstract
In the current study, amphiphilic peptides were designed and screened against Jack bean urease by using computer aided drug discovery approach. The result showed that out of thirty-eight amphiphilic peptides 1, 3, 12, 18, 30, and 33 exhibit stronger binding affinity with the active site of the enzyme through chelation of charged amino acids with the nickel ions i.e., Ni+2 841 and Ni+2 842 as well as hydrophobic contacts of the nonpolar tail with the nonpolar residues in the active site. The selected amphiphilic peptides were synthesized by solid-phase peptide synthesis strategy, characterized by fast atomic bombardment mass spectroscopy (FAB-MS) and nuclear magnetic resonance spectroscopy (1H and 13C-NMR) and in vitro urease inhibitory activity of amphiphilic peptides was studied. Amphiphilic peptides 12 and 33 showed excellent urease inhibitory activity, (p < 0.001) with IC50 values 20.5 ± 0.01, and 28.1 ± 0.03 µM respectively, which was considerably better than thiourea used as positive control.
Highlights
Nitrogen is essential component for the growth of pathogenic bacteria’s and plants, which is produced by urease enzyme from urea [1] The pathogens in large intestine of human being and animals hydrolyze urea into ammonia and carbamate by urease enzyme, which may cause adverse effects such as infectious stones, stomach ulcer, and peptic ulcer
It causes the pathogenesis of hepatic encephalopathy, pyelonephritis hepatic coma urolithiasis, ammonia, and urinary catheter encrustation [2,3,4]
The active site of this enzyme consists of two nickel ions (Ni 841 and Ni 842) having inter atomic distance of about 3.5 Ao, which are joined together by carbamylated lysine (KCX 490) and an oxygen donor
Summary
Nitrogen is essential component for the growth of pathogenic bacteria’s and plants, which is produced by urease enzyme from urea [1] The pathogens in large intestine of human being and animals hydrolyze urea into ammonia and carbamate by urease enzyme, which may cause adverse effects such as infectious stones, stomach ulcer, and peptic ulcer. It causes the pathogenesis of hepatic encephalopathy, pyelonephritis hepatic coma urolithiasis, ammonia, and urinary catheter encrustation [2,3,4]. Both Ni ions coordinated with two histidines (His 409) and a water molecule, while Ni2 has an addition coordination with aspartate (Asp 494) as shown in Fig. 1 [6]
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