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Exploration of CLP antitumor potential

Yentl Verleysen (UGent) , Matthias De Vleeschouwer (UGent) , Niels Geudens (UGent) , Marleen Van Troys (UGent) , Christophe Ampe (UGent) , Annemieke Madder (UGent) and José Martins (UGent)
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Abstract
Cyclic lipodepsipeptides (CLPs) are a class of secondary metabolites typically produced by Pseudomonas and Bacillus with interesting biological properties These amphiphilic compounds are composed of an oligopeptide chain, C-terminally cyclized through macrolactonization and N-terminally linked to a lipid tail. They exhibit substantial structural diversity as direct consequence of variation in amino acid composition, including modified proteinogenic, non-proteinogenic and D-amino acids, and the length and degree of saturation of the fatty acid moiety. CLPs receive considerable attention due to their broad range of biological activities including antibiotic, antiviral, antifungal and insecticidal properties. More recently, anticancer activity has been discovered as well. In spite of their potential in clinical and agricultural context, the molecular mechanism of action of most CLPs is yet to be determined, although it is clear that the cell membrane is an interaction partner and possibly the primary target. In order to exploit the promising properties of these compounds, establishment of their structure-activity relationship and a good understanding of their interaction with biological membranes at the molecular level, will be fundamental. Towards this, the site-specific and selective modification of CLPs for generation of molecular probes capable of exposing the mechanism of action represents an essential step forward.Over the last few years, considerable knowledge and expertise have been acquired when it comes to isolation, characterisation and synthesis of CLPs, the latter with emphasis on members of the viscosin group. For instance, a rapid and efficient total chemical synthesis strategy has been developed and optimized which already resulted in the successful synthesis of more than 30 compounds such as viscosin, pseudodesmin, WLIP and a wide variety of analogues thereof.[1–3] In addition, an NMR and modelling methodology was developed allowing a detailed understanding of CLP structure, conformational and self-assembly behaviour.[4–6] The unique combination of both expertise areas enables us to try and grasp the broader picture of CLP antitumor activity and tackle the problem of target identification and elucidation of the molecular events at a cellular level. References [1] M. De Vleeschouwer, J. C. M. and A. M. Davy Sinnaeve, Jos Van den Begin, Tom Coenye, Chem. - A Eur. J. 2014, 79, 1614–1621. [2] M. De Vleeschouwer, J. C. Martins, A. Madder, J. Pept. Sci. 2016, 22, 149–155. [3] M. De Vleeschouwer, D. Sinnaeve, N. Matthijs, T. Coenye, 2017, 640–644. [4] D. Sinnaeve, P. M. S. Hendrickx, J. Van Hemel, E. Peys, B. Kieffer, J. C. Martins, Chem. - A Eur. J. 2009, 15, 12653–12662. [5] N. Geudens, M. De Vleeschouwer, K. Fehér, H. Rokni-Zadeh, M. G. K. Ghequire, A. Madder, R. De Mot, J. C. Martins, D. Sinnaeve, ChemBioChem 2014, 15, 2736–2746. [6] N. Geudens, M. N. Nasir, J.-M. Crowet, J. M. Raaijmakers, K. Fehér, T. Coenye, J. C. Martins, L. Lins, D. Sinnaeve, M. Deleu, Biochim. Biophys. Acta - Biomembr. 2017, 1859, 331–339

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Chicago
Verleysen, Yentl, Matthias De Vleeschouwer, Niels Geudens, Marleen Van Troys, Christophe Ampe, Annemieke Madder, and José Martins. 2018. “Exploration of CLP Antitumor Potential.” In Belgian Peptide Group, 4th Meeting, Abstracts.
APA
Verleysen, Y., De Vleeschouwer, M., Geudens, N., Van Troys, M., Ampe, C., Madder, A., & Martins, J. (2018). Exploration of CLP antitumor potential. Belgian Peptide Group, 4th Meeting, Abstracts. Presented at the 4th Belgian Peptide Group meeting.
Vancouver
1.
Verleysen Y, De Vleeschouwer M, Geudens N, Van Troys M, Ampe C, Madder A, et al. Exploration of CLP antitumor potential. Belgian Peptide Group, 4th Meeting, Abstracts. 2018.
MLA
Verleysen, Yentl et al. “Exploration of CLP Antitumor Potential.” Belgian Peptide Group, 4th Meeting, Abstracts. 2018. Print.
@inproceedings{8601106,
  abstract     = {Cyclic lipodepsipeptides (CLPs) are a class of secondary metabolites typically produced by Pseudomonas and Bacillus with interesting biological properties These amphiphilic compounds are composed of an oligopeptide chain, C-terminally cyclized through macrolactonization and N-terminally linked to a lipid tail. They exhibit substantial structural diversity as direct consequence of variation in amino acid composition, including modified proteinogenic, non-proteinogenic and D-amino acids, and the length and degree of saturation of the fatty acid moiety. CLPs receive considerable attention due to their broad range of biological activities including antibiotic, antiviral, antifungal and insecticidal properties. More recently, anticancer activity has been discovered as well. In spite of their potential in clinical and agricultural context, the molecular mechanism of action of most CLPs is yet to be determined, although it is clear that the cell membrane is an interaction partner and possibly the primary target. In order to exploit the promising properties of these compounds, establishment of their structure-activity relationship and a good understanding of their interaction with biological membranes at the molecular level, will be fundamental. Towards this, the site-specific and selective modification of CLPs for generation of molecular probes capable of exposing the mechanism of action represents an essential step forward.Over the last few years, considerable knowledge and expertise have been acquired when it comes to isolation, characterisation and synthesis of CLPs, the latter with emphasis on members of the viscosin group. For instance, a rapid and efficient total chemical synthesis strategy has been developed and optimized which already resulted in the successful synthesis of more than 30 compounds such as viscosin, pseudodesmin, WLIP and a wide variety of analogues thereof.[1--3] In addition, an NMR and modelling methodology was developed allowing a detailed understanding of CLP structure, conformational and self-assembly behaviour.[4--6] The unique combination of both expertise areas enables us to try and grasp the broader picture of CLP antitumor activity and tackle the problem of target identification and elucidation of the molecular events at a cellular level.
References
[1] M. De Vleeschouwer, J. C. M. and A. M. Davy Sinnaeve, Jos Van den Begin, Tom Coenye, Chem. - A Eur. J. 2014, 79, 1614--1621.
[2] M. De Vleeschouwer, J. C. Martins, A. Madder, J. Pept. Sci. 2016, 22, 149--155.
[3] M. De Vleeschouwer, D. Sinnaeve, N. Matthijs, T. Coenye, 2017, 640--644.
[4] D. Sinnaeve, P. M. S. Hendrickx, J. Van Hemel, E. Peys, B. Kieffer, J. C. Martins, Chem. - A Eur. J. 2009, 15, 12653--12662.
[5] N. Geudens, M. De Vleeschouwer, K. Feh{\'e}r, H. Rokni-Zadeh, M. G. K. Ghequire, A. Madder, R. De Mot, J. C. Martins, D. Sinnaeve, ChemBioChem 2014, 15, 2736--2746.
[6] N. Geudens, M. N. Nasir, J.-M. Crowet, J. M. Raaijmakers, K. Feh{\'e}r, T. Coenye, J. C. Martins, L. Lins, D. Sinnaeve, M. Deleu, Biochim. Biophys. Acta - Biomembr. 2017, 1859, 331--339},
  author       = {Verleysen, Yentl and De Vleeschouwer, Matthias and Geudens, Niels and Van Troys, Marleen and Ampe, Christophe and Madder, Annemieke and Martins, Jos{\'e}},
  booktitle    = {Belgian Peptide Group, 4th Meeting, Abstracts},
  language     = {eng},
  location     = {Brussels, Belgium},
  title        = {Exploration of CLP antitumor potential},
  year         = {2018},
}