Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics

Serdar Kuyucak; Raymond Stanley Norton

doi:10.4155/FMC.14.98

Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics

Serdar Kuyucak, Raymond Stanley Norton

Medicinal Chemistry

Research output: Contribution to journal › Article › Research › peer-review

19 Citations (Scopus)

Abstract

Peptide toxins provide valuable therapeutic leads for many diseases. As they bind to their targets with high affinity, potency is usually ensured. However, toxins also bind to off-target receptors, causing potential side effects. Thus, a major challenge in generating drugs from peptide toxins is ensuring their specificity for their intended targets. Computational methods can play an important role in solving such design problems through construction of accurate models of receptor-toxin complexes and calculation of binding free energies. Here we review the computational methods used for this purpose and their application to toxins targeting ion channels. We describe ShK and HsTX1 toxins, high-affinity blockers of the voltage-gated potassium channel Kv1.3, which could be developed as therapeutic agents for autoimmune diseases.

Original language	English
Pages (from-to)	1645 - 1658
Number of pages	14
Journal	Future Medicinal Chemistry
Volume	6
Issue number	15
DOIs	https://doi.org/10.4155/FMC.14.98
Publication status	Published - 2014

Cite this

Kuyucak, S., & Norton, R. S. (2014). Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics. Future Medicinal Chemistry, 6(15), 1645 - 1658. https://doi.org/10.4155/FMC.14.98

Kuyucak, Serdar ; Norton, Raymond Stanley. / Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics. In: Future Medicinal Chemistry. 2014 ; Vol. 6, No. 15. pp. 1645 - 1658.

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Kuyucak, S & Norton, RS 2014, 'Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics', Future Medicinal Chemistry, vol. 6, no. 15, pp. 1645 - 1658. https://doi.org/10.4155/FMC.14.98

Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics. / Kuyucak, Serdar; Norton, Raymond Stanley.

In: Future Medicinal Chemistry, Vol. 6, No. 15, 2014, p. 1645 - 1658.

Research output: Contribution to journal › Article › Research › peer-review

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