Binding Interactions of Peptide Aptamers

Peptide aptamers are short amino acid chains that are capable of binding specifically to ligands in the same way as their much larger counterparts, antibodies. Ligands of therapeutic interest that can be targeted are other peptide chains or loops located on the surface of protein receptors (e.g., GCPR), which take part in cell-to-cell communications either directly or via the intermediary of hormones or signalling molecules. To confer on aptamers the same sort of conformational rigidity that characterises an antibody binding site, aptamers are often constructed in the form of cyclic peptides, on the assumption that this will encourage stronger binding interactions than would occur if the aptamers were simply linear chains. However, no formal studies have been conducted to confirm the hypothesis that linear peptides will engage in stronger binding interactions with cyclic peptides than with other linear peptides. In this study, the interaction of a model cyclic decamer with a series of linear peptide constructs was compared with that of a linear peptide with the same sequence, showing that the cyclic configuration does confer benefits by increasing the strength of binding.

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An antibody-binding site in the native enzyme between amino acid residues 205 – 287 of the γ -subunit of F1 from Escherichiacoli

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(86)91233-7 ◽

1986 ◽

Vol 137 (1) ◽

pp. 468-473 ◽

Cited By ~ 1

Author(s):

Karin Ehrig ◽

Jürgen Hoppe ◽

Peter Friedl ◽

Hans Ulrich Schairer

Keyword(s):

Amino Acid ◽

Binding Site ◽

Antibody Binding ◽

Native Enzyme ◽

Amino Acid Residues ◽

Antibody Binding Site ◽

Γ Subunit

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Synthetic RGD peptides derived from the adhesive domains of snake-venom proteins: evaluation as inhibitors of platelet aggregation

Biochemical Journal ◽

10.1042/bj2960021 ◽

1993 ◽

Vol 296 (1) ◽

pp. 21-24 ◽

Cited By ~ 15

Author(s):

X Lu ◽

J J Deadman ◽

J A Williams ◽

V V Kakkar ◽

S Rahman

Keyword(s):

Amino Acid ◽

Platelet Aggregation ◽

Cyclic Peptides ◽

Platelet Aggregation Inhibitors ◽

Cyclic Form ◽

Rgd Peptides ◽

Linear Peptide ◽

Parent Protein ◽

Aggregation Inhibitors ◽

Venom Proteins

Synthetic peptides based on the RGD domains of the potent platelet aggregation inhibitors kistrin and dendroaspin were generated. The 13-amino-acid peptides were synthesized as dicysteinyl linear and disulphide cyclic forms. In platelet-aggregation studies, the cyclic peptides showed 3-fold better inhibition than their linear equivalents and approx. 100-fold greater potency than synthetic linear RGDS peptides derived from fibronectin. An amino acid substitution, Asp10→Ala, in the kistrin-based peptide gave a 4-fold decrease in potency in the linear peptide, but produced a 2-fold elevation in the inhibitory activity of the cyclic form, generating a peptide of potency comparable with that of the parent protein.

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Development of peptides targeting receptor binding site of the envelope glycoprotein to contain the West Nile virus infection

Scientific Reports ◽

10.1038/s41598-021-99696-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Patrícia Mertinková ◽

Evelína Mochnáčová ◽

Katarína Bhide ◽

Amod Kulkarni ◽

Zuzana Tkáčová ◽

...

Keyword(s):

West Nile Virus ◽

Binding Site ◽

Receptor Binding ◽

Cyclic Peptides ◽

Cultured Cells ◽

West Nile Virus Infection ◽

Building Blocks ◽

West Nile ◽

Receptor Binding Site ◽

Linear Peptide

AbstractWest Nile virus (WNV), re-emerging neurotropic flavivirus, can cross the blood–brain barrier (BBB) and cause fatal encephalitis and meningitis. Infection of the human brain microvascular endothelial cells (hBMECs), building blocks of the BBB, represents the pivotal step in neuroinvasion. Domain III (DIII) of the envelope (E) glycoprotein is a key receptor-binding domain, thus, it is an attractive target for anti-flavivirus strategies. Here, two combinatorial phage display peptide libraries, Ph.D.-C7C and Ph.D.-12, were panned against receptor-binding site (RBS) on DIII to isolate peptides that could block DIII. From series of pannings, nine peptides (seven 7-mer cyclic and two 12-mer linear) were selected and overexpressed in E. coli SHuffle T5. Presence of disulfide bond in 7-mer peptides was confirmed with thiol-reactive maleimide labeling. Except for linear peptide 19 (HYSWSWIAYSPG), all peptides proved to be DIII binders. Among all peptides, 4 cyclic peptides (CTKTDVHFC, CIHSSTRAC, CTYENHRTC, and CLAQSHPLC) showed significant blocking of the interaction between DIII and hBMECs, and ability to neutralize infection in cultured cells. None of these peptides showed toxic or hemolytic activity. Peptides identified in this study may serve as potential candidates for the development of novel antiviral therapeutics against WNV.

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Faculty Opinions recommendation of Self-assembling peptide nanotubes from enantiomeric pairs of cyclic peptides with alternating D and L amino acid residues.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018033.206566 ◽

2004 ◽

Author(s):

James Nowick

Keyword(s):

Amino Acid ◽

Cyclic Peptides ◽

Amino Acid Residues ◽

Peptide Nanotubes ◽

Self Assembling

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Schistosomal Sulfotransferase Interaction with Oxamniquine Involves Hybrid Mechanism of Induced-fit and Conformational Selection

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190708103132 ◽

2020 ◽

Vol 16 (4) ◽

pp. 451-459 ◽

Cited By ~ 1

Author(s):

Fortunatus C. Ezebuo ◽

Ikemefuna C. Uzochukwu

Keyword(s):

Molecular Dynamics ◽

Amino Acid ◽

Binding Energy ◽

Binding Site ◽

Conformational Dynamics ◽

Side Chain ◽

Amino Acid Residues ◽

Conformational Selection ◽

Hybrid Mechanism ◽

Dynamics Simulations

Background: Sulfotransferase family comprises key enzymes involved in drug metabolism. Oxamniquine is a pro-drug converted into its active form by schistosomal sulfotransferase. The conformational dynamics of side-chain amino acid residues at the binding site of schistosomal sulfotransferase towards activation of oxamniquine has not received attention. Objective: The study investigated the conformational dynamics of binding site residues in free and oxamniquine bound schistosomal sulfotransferase systems and their contribution to the mechanism of oxamniquine activation by schistosomal sulfotransferase using molecular dynamics simulations and binding energy calculations. Methods: Schistosomal sulfotransferase was obtained from Protein Data Bank and both the free and oxamniquine bound forms were subjected to molecular dynamics simulations using GROMACS-4.5.5 after modeling it’s missing amino acid residues with SWISS-MODEL. Amino acid residues at its binding site for oxamniquine was determined and used for Principal Component Analysis and calculations of side-chain dihedrals. In addition, binding energy of the oxamniquine bound system was calculated using g_MMPBSA. Results: The results showed that binding site amino acid residues in free and oxamniquine bound sulfotransferase sampled different conformational space involving several rotameric states. Importantly, Phe45, Ile145 and Leu241 generated newly induced conformations, whereas Phe41 exhibited shift in equilibrium of its conformational distribution. In addition, the result showed binding energy of -130.091 ± 8.800 KJ/mol and Phe45 contributed -9.8576 KJ/mol. Conclusion: The results showed that schistosomal sulfotransferase binds oxamniquine by relying on hybrid mechanism of induced fit and conformational selection models. The findings offer new insight into sulfotransferase engineering and design of new drugs that target sulfotransferase.

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Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site.

Journal of Virology ◽

10.1128/jvi.57.1.81-90.1986 ◽

1986 ◽

Vol 57 (1) ◽

pp. 81-90 ◽

Cited By ~ 65

Author(s):

B Blondel ◽

R Crainic ◽

O Fichot ◽

G Dufraisse ◽

A Candrea ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Binding Site ◽

Antibody Binding ◽

Antibody Binding Site

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Synthesis of Fragments of the Vasoactive Intestinal Peptide (VIP) and Analysis of Their Residual Biological Activities

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19951229 ◽

1995 ◽

Vol 60 (7) ◽

pp. 1229-1235 ◽

Cited By ~ 2

Author(s):

Ivana Zoulíková ◽

Ivan Svoboda ◽

Jiří Velek ◽

Václav Kašička ◽

Jiřina Slaninová ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Residual Activity ◽

Detailed Examination ◽

Amino Acid Residues ◽

Linear Peptide ◽

Zone Electrophoresis ◽

Capillary Zone

The vasoactive intestinal (poly)peptide (VIP) is a linear peptide containing 28 amino acid residues, whose primary structure indicates a low metabolic stability. The following VIP fragments, as potential metabolites, and their analogues were prepared by synthesis on a solid: [His(Dnp)1]VIP(1-10), VIP(11-14), [D-Arg12]VIP(11-14), [Lys(Pac)15,21,Arg20]VIP(15-22), and VIP(23-28). After purification, the peptides were characterized by amino acid analysis, mass spectrometry, RP HPLC, and capillary zone electrophoresis. In some tests, detailed examination of the biological activity of the substances in vivo and in vitro gave evidence of a low, residual activity of some fragments, viz. a depressoric activity in vivo for [His(Dnp)1]VIP(1-10) and a stimulating activity for the release of α-amylase in vitro and in vivo for [Lys(Pac)15,21,Arg20]VIP(15-22) and VIP(23-28).

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Mitigating the Adverse Effects of Polychlorinated Biphenyl Derivatives on Estrogenic Activity via Molecular Modification Techniques

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094999 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4999

Author(s):

Wei He ◽

Wenhui Zhang ◽

Zhenhua Chu ◽

Yu Li

Keyword(s):

Amino Acid ◽

Binding Site ◽

Hydrophobic Interaction ◽

Oestrogen Receptor ◽

Polychlorinated Biphenyl ◽

Hydrophobic Interactions ◽

Estrogenic Activity ◽

Average Distance ◽

Amino Acid Residues ◽

Hydrophobic Amino Acid

The aim of this paper is to explore the mechanism of the change in oestrogenic activity of PCBs molecules before and after modification by designing new PCBs derivatives in combination with molecular docking techniques through the constructed model of oestrogenic activity of PCBs molecules. We found that the weakened hydrophobic interaction between the hydrophobic amino acid residues and hydrophobic substituents at the binding site of PCB derivatives and human oestrogen receptor alpha (hERα) was the main reason for the weakened binding force and reduced anti-oestrogenic activity. It was consistent with the information that the hydrophobic field displayed by the 3D contour maps in the constructed oestrogen activity CoMSIA model was one of the main influencing force fields. The hydrophobic interaction between PCB derivatives and oestrogen-active receptors was negatively correlated with the average distance between hydrophobic substituents and hydrophobic amino acid residues at the hERα-binding site, and positively correlated with the number of hydrophobic amino acid residues. In other words, the smaller the average distance between the hydrophobic amino acid residues at the binding sites between the two and the more the number of them, and the stronger the oestrogen activity expression degree of PCBS derivative molecules. Therefore, hydrophobic interactions between PCB derivatives and the oestrogen receptor can be reduced by altering the microenvironmental conditions in humans. This reduces the ability of PCB derivatives to bind to the oestrogen receptor and can effectively modulate the risk of residual PCB derivatives to produce oestrogenic activity in humans.

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