Prolylendopeptidase Inhibitory Activity of a Glial Fibrillary Acidic Protein Fragment and Other Proline-rich Peptides

Maruyama, Susumu; Ohmori, Takashi; Nakagami, Tatsuyoshi

doi:10.1271/bbb.60.358

Cited by 11 publications

(1 citation statement)

References 3 publications

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“…In fact, YPG was more potent as DPP-IV inhibitor than a number of other tripeptides WWW, LPL, LQP, IQP and VGL reported with DPP-IV inhibitory activity [29]. To the best of our knowledge, apart from IPI, IPM, LPQ and VPL [29,30,32,33], no other tripeptide with higher DPP-IV inhibitory than YPG could be found after searching the entire BIOPEP database (http://www.uwm.edu.pl/biochemia/index.php/en/biopep). The IPI is a known DPP-IV inhibitory peptide commonly used as positive control [29,30].…”

Section: Discussionmentioning

confidence: 68%

Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal

Ibrahim

Serem

Bester

et al. 2019

International Journal of Biological Macromolecules

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Highlights• The peptides PFP, YPL and YPG were investigated for multiple antidiabetic effects.• In vitro, the peptides inhibited dipeptidyl peptidase-4 but YPG was the best.• YPG was the best in preventing lipid accumulation in 3T3-L1 differentiated adipocytes.• Along with other parameters, YPG is the best multifunctional antidiabetic candidate. ABSTRACTAntidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP < YPG < YPL < diprotin A while hydrogen bond interactions were critical in the binding of YPL and YPG. Moreover, YPG demonstrated significantly higher (p<0.05) in vitro DPP-IV inhibition than PFP and YPL. Kinetic analysis revealed that all three peptides are uncompetitive inhibitors of DPP-IV while YPG had the lowest inhibition binding constant. PFP and YPG prevented lipid accumulation in 3T3-L1 differentiated adipocytes but may be due to cytotoxicity for PFP. The peptides scavenged MGO, ROS and NO but only the ROS and NO scavenging activities of YPG were comparable to glutathione. In conclusion, PFP, YPL and YPG exhibited DPP-IV inhibitory activity, reduced adipocyte differentiation and lipid accumulation as well as scavenged MGO, ROS and NO. However, YPG had the best potential as a possible multifunctional antidiabetic agent.

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