Application of phage display for the development of a novel inhibitor of PLA2 activity in western cottonmouth venom

Titus, James K; Kay, Matthew; Glaser, Jacob; Hwang, Young Hwan

doi:10.1016/j.toxicon.2018.10.124

Cited by 9 publications

(10 citation statements)

References 16 publications

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“…One of these binders was further tested against venom from A. p. leucostoma (again), Crotalus adamanteus, Crotalus atrox, Crotalus scutulatus, and Agkistrodon contortrix laticinctus using the same assay. Inhibition of PLA2 activities of these venoms was, however, only 30-40% [35], which leaves much room for improvement. Given that linear peptides typically have a poor half-life, much more work is needed before any analogues of the reported peptides may become as promising as varespladib.…”

Section: Small Molecule Inhibitors and Peptidesmentioning

confidence: 97%

“…Using one of the same peptide phage display libraries as Laustsen [34], Titus et al employed phage display to find binders for a consensus PLA2 [35]. The PLA2 was based on a consensus sequence derived from alignments of available sequences of Agkistrodon PLA2s and mapped to an Agkistrodon piscivorus piscivorus PLA2 structure, before being synthesised.…”

Section: Small Molecule Inhibitors and Peptidesmentioning

confidence: 99%

See 1 more Smart Citation

Recent Advances in Next Generation Snakebite Antivenoms

Knudsen¹,

Laustsen²

2018

Preprint

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With the inclusion of snakebite envenoming on the World Health Organisation’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Different technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins, as well as peptide and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors, varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.

show abstract

Section: Small Molecule Inhibitors and Peptidesmentioning

confidence: 97%

Section: Small Molecule Inhibitors and Peptidesmentioning

confidence: 99%

Recent Advances in Next Generation Snakebite Antivenoms

Knudsen¹,

Laustsen²

2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Using one of the same peptide phage display libraries as Laustsen [ 42 ], Titus et al employed phage display to find binders for a consensus PLA 2 [ 43 ]. The PLA 2 was based on a consensus sequence derived from alignments of available sequences of Agkistrodon PLA 2 s and mapped to an Agkistrodon piscivorus piscivorus PLA 2 structure before being synthesised.…”

Section: Small Molecule Inhibitors and Peptidesmentioning

confidence: 99%

“…One of these binders was further tested against venom from A. p. leucostoma (again), Crotalus adamanteus, Crotalus atrox, Crotalus scutulatus , and Agkistrodon contortrix laticinctus using the same assay. Inhibition of PLA 2 activities of these venoms was, however, only 30–40% [ 43 ], which leaves much room for improvement. Given that linear peptides typically have a poor half-life, much more work is needed before any analogues of the reported peptides may become as promising as varespladib.…”

Section: Small Molecule Inhibitors and Peptidesmentioning

confidence: 99%

Recent Advances in Next Generation Snakebite Antivenoms

Knudsen

Laustsen

2018

TropicalMed

View full text Add to dashboard Cite

With the inclusion of snakebite envenoming on the World Health Organization’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Various technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins as well as peptide- and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.

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“…Phage display has also been exploited for the discovery of snake anti-venom peptides. A study has shown that peptides against Phospholipase A 2 (PLA 2 ) inhibits PLA 2 activity of the venom of western cottonmouth [80].…”

Section: Other Therapeutic Applicationmentioning

confidence: 99%

Clinical implications of phage display technique: Digging deeper in diagnostic and therapeutic grounds.

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Phage display is considered as a gold-standard technique for the extraction of monoclonal antibodies. Within the past decade, the technique has been extensively applied in clinical studies for the discovery of peptides, ligands and antibodies that can be implemented for the detection of clinical biomarkers and therapeutic purposes. This review highlights recent advancements in the field of phage display technology that has aided medicine in therapeutic and diagnostic terms.

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Application of phage display for the development of a novel inhibitor of PLA2 activity in western cottonmouth venom

Cited by 9 publications

References 16 publications

Recent Advances in Next Generation Snakebite Antivenoms

Recent Advances in Next Generation Snakebite Antivenoms

Recent Advances in Next Generation Snakebite Antivenoms

Clinical implications of phage display technique: Digging deeper in diagnostic and therapeutic grounds.

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