Discovery of Peptide Drugs as Enzyme Inhibitors and Activators

Nguyen, Jeffrey‐Tri; Kiso, Yoshiaki

doi:10.1002/9781118995303.ch5

Cited by 1 publication

(2 citation statements)

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“…High-throughput screening (HTS) has been widely used to search large libraries of small molecules, peptides, and nucleic acids for identifying potential ligands that can bind with a protein target to modulate its function. , Peptides are promising ligands for modulating protein functions because of their large chemical diversity and well-established methods of library synthesis . Peptides and their derivatives have already been used to inhibit a variety of enzymes, like dehydrogenase, protein kinase, and protease . Cell-permeable peptides can be used to block and regulate cellular signaling pathways .…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Peptides are promising ligands for modulating protein functions 6 because of their large chemical diversity 7 and well-established methods of library synthesis. 8 Peptides and their derivatives have already been used to inhibit a variety of enzymes, 9 like dehydrogenase, 10 protein kinase, 11 and protease. 12 Cell-permeable peptides can be used to block and regulate cellular signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

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Reduction of Promiscuous Peptides-Enzyme Inhibition and Aggregation by Negatively Charged Biopolymers

Nguyen

2022

ACS Appl. Bio Mater.

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In this work, peptides selected from a microarray were found to inhibit β-gal with promiscuous mechanisms. Peptides inhibited the enzyme in a noncompetitive kinetics, and the inhibition of enzyme activities was reduced under high enzyme concentrations and the addition of detergent. Dynamic light scattering and atomic force microscope revealed that peptide/enzyme aggregation was related to inhibited enzyme activities. Positively charged residues of arginine and lysine were critical for the enzyme inhibition. The preincubation of peptide inhibitors with negatively charged biopolymers of polyphosphates, ssDNA, and low pI peptides could increase the residual activity of peptide-inhibited enzyme, possibly due to the disruption of the electrostatic interaction between positively charged peptide residues and the β-gal surface. Further, negative biopolymers were able to recover the activity of the aggregated peptide/β-gal complex. Negatively charged biopolymers could be used in high-throughput screening assays to reduce peptides/protein aggregation and thereby minimize promiscuous inhibitions.

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