Cargando…
Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma
The study investigates the antitumor effect of two cationic peptides, R-DIM-P-LF11-215 (RDP215) and the D-amino acid variant 9D-R-DIM-P-LF11-215 (9D-RDP215), targeting the negatively charged lipid phosphatidylserine (PS) exposed by cancer cells, such as of melanoma and glioblastoma. Model studies mi...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395111/ https://www.ncbi.nlm.nih.gov/pubmed/34445175 http://dx.doi.org/10.3390/ijms22168469 |
_version_ | 1783744098742566912 |
---|---|
author | Maxian, Theresa Gerlitz, Lisa Riedl, Sabrina Rinner, Beate Zweytick, Dagmar |
author_facet | Maxian, Theresa Gerlitz, Lisa Riedl, Sabrina Rinner, Beate Zweytick, Dagmar |
author_sort | Maxian, Theresa |
collection | PubMed |
description | The study investigates the antitumor effect of two cationic peptides, R-DIM-P-LF11-215 (RDP215) and the D-amino acid variant 9D-R-DIM-P-LF11-215 (9D-RDP215), targeting the negatively charged lipid phosphatidylserine (PS) exposed by cancer cells, such as of melanoma and glioblastoma. Model studies mimicking cancer and non-cancer membranes revealed the specificity for the cancer-mimic PS by both peptides with a slightly stronger impact by the D-peptide. Accordingly, membrane effects studied by DSC, leakage and quenching experiments were solely induced by the peptides when the cancer mimic PS was present. Circular dichroism revealed a sole increase in β-sheet conformation in the presence of the cancer mimic for both peptides; only 9D-RDP215 showed increased structure already in the buffer. Ex vitro stability studies by SDS-PAGE as well as in vitro with melanoma A375 revealed a stabilizing effect of D-amino acids in the presence of serum, which was also confirmed in 2D and 3D in vitro experiments on glioblastoma LN-229. 9D-RDP215 was additionally able to pass a BBB model, whereupon it induced significant levels of cell death in LN-229 spheroids. Summarized, the study encourages the introduction of D-amino acids in the design of antitumor peptides for the improvement of their stable antitumor activity. |
format | Online Article Text |
id | pubmed-8395111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83951112021-08-28 Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma Maxian, Theresa Gerlitz, Lisa Riedl, Sabrina Rinner, Beate Zweytick, Dagmar Int J Mol Sci Article The study investigates the antitumor effect of two cationic peptides, R-DIM-P-LF11-215 (RDP215) and the D-amino acid variant 9D-R-DIM-P-LF11-215 (9D-RDP215), targeting the negatively charged lipid phosphatidylserine (PS) exposed by cancer cells, such as of melanoma and glioblastoma. Model studies mimicking cancer and non-cancer membranes revealed the specificity for the cancer-mimic PS by both peptides with a slightly stronger impact by the D-peptide. Accordingly, membrane effects studied by DSC, leakage and quenching experiments were solely induced by the peptides when the cancer mimic PS was present. Circular dichroism revealed a sole increase in β-sheet conformation in the presence of the cancer mimic for both peptides; only 9D-RDP215 showed increased structure already in the buffer. Ex vitro stability studies by SDS-PAGE as well as in vitro with melanoma A375 revealed a stabilizing effect of D-amino acids in the presence of serum, which was also confirmed in 2D and 3D in vitro experiments on glioblastoma LN-229. 9D-RDP215 was additionally able to pass a BBB model, whereupon it induced significant levels of cell death in LN-229 spheroids. Summarized, the study encourages the introduction of D-amino acids in the design of antitumor peptides for the improvement of their stable antitumor activity. MDPI 2021-08-06 /pmc/articles/PMC8395111/ /pubmed/34445175 http://dx.doi.org/10.3390/ijms22168469 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maxian, Theresa Gerlitz, Lisa Riedl, Sabrina Rinner, Beate Zweytick, Dagmar Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma |
title | Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma |
title_full | Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma |
title_fullStr | Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma |
title_full_unstemmed | Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma |
title_short | Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma |
title_sort | effect of l- to d-amino acid substitution on stability and activity of antitumor peptide rdp215 against human melanoma and glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395111/ https://www.ncbi.nlm.nih.gov/pubmed/34445175 http://dx.doi.org/10.3390/ijms22168469 |
work_keys_str_mv | AT maxiantheresa effectofltodaminoacidsubstitutiononstabilityandactivityofantitumorpeptiderdp215againsthumanmelanomaandglioblastoma AT gerlitzlisa effectofltodaminoacidsubstitutiononstabilityandactivityofantitumorpeptiderdp215againsthumanmelanomaandglioblastoma AT riedlsabrina effectofltodaminoacidsubstitutiononstabilityandactivityofantitumorpeptiderdp215againsthumanmelanomaandglioblastoma AT rinnerbeate effectofltodaminoacidsubstitutiononstabilityandactivityofantitumorpeptiderdp215againsthumanmelanomaandglioblastoma AT zweytickdagmar effectofltodaminoacidsubstitutiononstabilityandactivityofantitumorpeptiderdp215againsthumanmelanomaandglioblastoma |