1. Sequence dependent folding motifs of the secondary structures of Gly-Pro and Pro-Gly containing oligopeptides
Satish Kumar, Kshetrimayum Borish, Sanjit Dey, Jayashree Nagesh, Aloke Das Phys Chem Chem Phys. 2022 Aug 3;24(30):18408-18418. doi: 10.1039/d2cp01306a.
Folding motifs of the secondary structures of peptides and proteins are primarily based on the hydrogen bonding interactions in the backbone as well as the sequence of the amino acid residues present. For instance, the β-turn structure directed by the Pro-Gly sequence is the key to the β-hairpin structure of peptides/proteins as well as a selective site for the enzymatic hydroxylation of pro-collagen. Herein, we have investigated the sequence dependent folding motifs of end-protected Gly-Pro and Pro-Gly dipeptides using a combination of gas phase laser spectroscopy, quantum chemistry calculations, solution phase IR and NMR spectroscopy and single crystal X-Ray diffraction (XRD). All three observed conformers of the Gly-Pro peptide in the gas phase have been found to have extended β-strand or polyproline-II (PP-II) structures with C5-C7 hydrogen bonding interactions, which correlates well with the structure obtained from solution phase spectroscopy and XRD. On the other hand, we have found that the Pro-Gly peptide has a C10/β-turn structure in the solution phase in contrast to the C7-C7 (i.e. 27-ribbon) structure observed in the gas phase. Although the lowest energy structure in the gas phase is not C10, we find that C7-C7 is an abundantly found structural motif of Pro-Gly containing peptides in the Cambridge Structural Database, indicating that the gas phase conformers are not sampling any unusual forms. We surmise that the role of the solvent could be crucial in dictating the preferential stabilization of the C10 structure in the solution phase. The present investigation provides a comprehensive picture of the folding motifs of the Gly-Pro and Pro-Gly peptides observed in the gas phase and condensed phase weaving a fine interplay of the intrinsic conformational properties, solvation, and crystal packing of the peptides.
2. The Pro-Gly or Hyp-Gly Containing Peptides from Absorbates of Fish Skin Collagen Hydrolysates Inhibit Platelet Aggregation and Target P2Y12 Receptor by Molecular Docking
Qi Tian, Shi-Ming Li, Bo Li Foods. 2021 Jul 5;10(7):1553. doi: 10.3390/foods10071553.
Previous studies found that the collagen hydrolysates of fish skin have antiplatelet activity, but this component remained unknown. In this study, eleven peptides were isolated and identified in the absorbates of Alcalase-hydrolysates and Protamex®-hydrolysates of skin collagen of H. Molitrix by reverse-phase C18 column and HPLC-MS/MS. Nine of them contained a Pro-Gly (PG) or Hyp-Gly (OG) sequence and significantly inhibited ADP-induced platelet aggregation in vitro, which suggested that the PG(OG) sequence is the core sequence of collagen peptides with antiplatelet activity. Among them, OGSA has the strongest inhibiting activities against ADP-induced platelet aggregation in vitro (IC50 = 0.63 mM), and OGSA inhibited the thrombus formation in rats at a dose of 200 μM/kg.bw with no risk of bleeding. The molecular docking results implied that the OG-containing peptides might target the P2Y12 receptor and form hydrogen bonds with the key sites Cys97, Ser101, and Lys179. As the sequence PG(OG) is abundant in the collagen amino acid sequence of H. Molitrix, the collagen hydrolysates of H. Molitrix might have great potential for being developed as dietary supplements to prevent cardiovascular diseases in the future.
3. ACTH(6-9)-Pro-Gly-Pro ameliorates anxiety-like and depressive-like behaviour and gut mucosal microbiota composition in rats under conditions of chronic restraint stress
Anton O Vorvul, et al. Neuropeptides. 2022 Jun;93:102247. doi: 10.1016/j.npep.2022.102247. Epub 2022 Apr 21.
The effects of the peptide ACTH(6-9)-Pro-Gly-Pro at doses of 5; 50; 500 μg/kg on the Wistar rats' behaviour and gut mucosal microbiota composition under conditions of chronic immobilization stress (CRS) were studied. CRS increased anxiety-like and depressive-like behaviour, disturbances in locomotor activity and gut dysbiosis. Administration of ACTH(6-9)-Pro-Gly-Pro showed many phenotypic results. Peptide demonstrated anti-depressant activity at doses of 5 and 500 μg/kg by a decrease in the total immobile time in the FST. ACTH(6-9)-Pro-Gly-Pro administered at a dose of 50 μg/kg resulted in an anxiolytic effect which is shown by an increase in the time in the open arms of EPM (p < 0.05) and a decrease in the time in the closed arms (p < 0.05). Moreover, the peptide led to a decrease in alpha- and beta-diversity of the gut microbiota (p < 0.01). Correlation and linear regression analysis demonstrated central mechanisms of ACTH(6-9)-Pro-Gly-Pro anxiolytic activity and both central and peripheral ones in an anti-depressant effect. In this way, peptide ACTH(6-9)-Pro-Gly-Pro could prevent the development of behavioural disturbances and gut dysbiosis caused by chronic restraint stress.
