Design, optimization and evaluation of specific affinity adsorbent for oligopeptides

Qiao, Yitao; Li, Pinglin; Chen, Yingchao; Feng, Jing; Wang, Jun; Wang, Wei; Ma, Yangmin; Sun, Pingchuan; Yuan, Zhi

doi:10.1016/j.chroma.2010.10.007

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…It is well-known that the interaction between proteins is based on the synergistic action of multiple weak interactions . Therefore, we speculated that if inhibitors can target several regions through multiple recognition and binding sites, the binding affinity between the inhibitor and Aβ would be enhanced and the inhibition of Aβ aggregation would be more effective .…”

Section: Introductionmentioning

confidence: 99%

“…It is well-known that the interaction between proteins is based on the synergistic action of multiple weak interactions. 38 Therefore, we speculated that if inhibitors can target several regions through multiple recognition and binding sites, the binding affinity between the inhibitor and Aβ would be enhanced and the inhibition of Aβ aggregation would be more effective. 39 On the basis of the studies described above, we designed a decapeptide inhibitor RR (RYYAAFFARR) with the help of computer simulation based on the structure of the Aβ 11−23 region, which is expected to interact with Aβ 1−40 in multiple ways, including via hydrophobic and electrostatic interactions and hydrogen bonding (Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

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Study on the Efficiency and Interaction Mechanism of a Decapeptide Inhibitor of β-Amyloid Aggregation

et al. 2014

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This paper reports an active decapeptide inhibitor (RR: RYYAAFFARR) of β-amyloid (Aβ(1-40)) aggregation. Traditional inhibitors target the hydrophobic core of Aβ (Aβ(16-20)) and were designed based on the single hydrophobic interaction. RR was designed to target an extended region (Aβ(11-23)), which contains three important regions of Aβ(1-40). RR exhibits stronger binding affinity for Aβ(1-40) (K(D) = 1.10 μM) than the known β-sheet breaker LPFFD (K(D) = 156 μM). Our study shows that RR inhibited the fibrillation of Aβ(1-40) by nearly 75% at an equimolar concentration, and that a 1:4 ratio of Aβ(1-40)/ RR almost completely inhibited fibrillation. The interaction mechanism was also investigated by changing the ionic strength or the structure of RR. The results revealed that RR binds to Aβ(1-40) because of its strong affinity for Aβ(11-23), which is mainly driven by hydrophobic and electrostatic interactions and hydrogen bonding.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Study on the Efficiency and Interaction Mechanism of a Decapeptide Inhibitor of β-Amyloid Aggregation

et al. 2014

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Ligand Design

Wan¹

2021

Mixed-Mode Chromatography

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Combined docking, molecular dynamics simulations and spectroscopic studies for the rational design of a dipeptide ligand for affinity chromatography separation of human serum albumin

et al. 2014

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A computational approach to designing a peptide-based ligand for the purification of human serum albumin (HSA) was undertaken using molecular docking and molecular dynamics (MD) simulation. A three-step procedure was performed to design a specific ligand for HSA. Based on the candidate pocket structure of HSA (warfarin binding site), a peptide library was built. These peptides were then docked into the pocket of HSA using the GOLD program. The GOLDscore values were used to determine the affinity of peptides for HSA. Consequently, the dipeptide Trp-Trp, which shows a high GOLDscore value, was selected and linked to a spacer arm of Lys[CO(CH2)5NH] on the surface of ECH-lysine sepharose 4 gel. For further evaluation, the Autodock Vina program was used to dock the linked compound into the pocket of HSA. The docking simulation was performed to obtain a first guess of the binding structure of the spacer-Trp-Trp-HSA complex and subsequently analyzed by MD simulations to assess the reliability of the docking results. These MD simulations indicated that the ligand-HSA complex remains stable, and water molecules can bridge between the ligand and the protein by hydrogen bonds. Finally, absorption spectroscopic studies were performed to illustrate the appropriateness of the binding affinity of the designed ligand toward HSA. These studies demonstrate that the designed dipeptide can bind preferentially to the warfarin binding site.

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Design, optimization and evaluation of specific affinity adsorbent for oligopeptides

Cited by 3 publications

References 26 publications

Study on the Efficiency and Interaction Mechanism of a Decapeptide Inhibitor of β-Amyloid Aggregation

Study on the Efficiency and Interaction Mechanism of a Decapeptide Inhibitor of β-Amyloid Aggregation

Ligand Design

Combined docking, molecular dynamics simulations and spectroscopic studies for the rational design of a dipeptide ligand for affinity chromatography separation of human serum albumin

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