Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

A series of small synthetic arginine and tryptophan containing peptides was prepared and analyzed for their antibacterial activity. The effect of N-terminal substitution with metallocenoyl groups such as ferrocene (FcCO) and ruthenocene (RcCO) was investigated. Antibacterial activity in different me...

Full description

Bibliographic Details
Main Authors:	Albada, H Bauke, Chiriac, Alina-Iulia, Wenzel, Michaela, Penkova, Maya, Bandow, Julia E, Sahl, Hans-Georg, Metzler-Nolte, Nils
Format:	Online
Language:	English
Published:	Beilstein-Institut 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511009/

id	pubmed-3511009
recordtype	oai_dc
spelling	pubmed-35110092012-12-03 Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups Albada, H Bauke Chiriac, Alina-Iulia Wenzel, Michaela Penkova, Maya Bandow, Julia E Sahl, Hans-Georg Metzler-Nolte, Nils Full Research Paper A series of small synthetic arginine and tryptophan containing peptides was prepared and analyzed for their antibacterial activity. The effect of N-terminal substitution with metallocenoyl groups such as ferrocene (FcCO) and ruthenocene (RcCO) was investigated. Antibacterial activity in different media, growth inhibition, and killing kinetics of the most active peptides were determined. The toxicity of selected derivatives was determined against erythrocytes and three human cancer cell lines. It was shown that the replacement of an N-terminal arginine residue with a metallocenoyl moiety modulates the activity of WRWRW-peptides against Gram-positive and Gram-negative bacteria. MIC values of 2–6 µM for RcCO-W(RW)2 and 1–11 µM for (RW)3 were determined. Interestingly, W(RW)2-peptides derivatized with ferrocene were significantly less active than those derivatized with ruthenocene which have similar structural but different electronic properties, suggesting a major influence of the latter. The high activities observed for the RcCO-W(RW)2- and (RW)3-peptides led to an investigation of the origin of activity of these peptides using several important activity-related parameters. Firstly, killing kinetics of the RcCO-W(RW)2-peptide versus killing kinetics of the (RW)3 derivative showed faster reduction of the colony forming units for the RcCO-W(RW)2-peptide, although MIC values indicated higher activity for the (RW)3-peptide. This was confirmed by growth inhibition studies. Secondly, hemolysis studies revealed that both peptides did not lead to significant destruction of erythrocytes, even up to 500 µg/mL for (RW)3 and 250 µg/mL for RcCO-W(RW)2. In addition, toxicity against three human cancer cell lines (HepG2, HT29, MCF7) showed that the (RW)3-peptide had an IC50 value of ~140 µM and the RcW(RW)2 one of ~90 µM, indicating a potentially interesting therapeutic window. Both the killing kinetics and growth inhibition studies presented in this work point to a membrane-based mode of action for these two peptides, each having different kinetic parameters. Beilstein-Institut 2012-10-15 /pmc/articles/PMC3511009/ /pubmed/23209509 http://dx.doi.org/10.3762/bjoc.8.200 Text en Copyright © 2012, Albada et al; licensee Beilstein-Institut. http://www.beilstein-journals.org/bjoc This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc)
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Albada, H Bauke Chiriac, Alina-Iulia Wenzel, Michaela Penkova, Maya Bandow, Julia E Sahl, Hans-Georg Metzler-Nolte, Nils
spellingShingle	Albada, H Bauke Chiriac, Alina-Iulia Wenzel, Michaela Penkova, Maya Bandow, Julia E Sahl, Hans-Georg Metzler-Nolte, Nils Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups
author_facet	Albada, H Bauke Chiriac, Alina-Iulia Wenzel, Michaela Penkova, Maya Bandow, Julia E Sahl, Hans-Georg Metzler-Nolte, Nils
author_sort	Albada, H Bauke
title	Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups
title_short	Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups
title_full	Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups
title_fullStr	Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups
title_full_unstemmed	Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups
title_sort	modulating the activity of short arginine-tryptophan containing antibacterial peptides with n-terminal metallocenoyl groups
description	A series of small synthetic arginine and tryptophan containing peptides was prepared and analyzed for their antibacterial activity. The effect of N-terminal substitution with metallocenoyl groups such as ferrocene (FcCO) and ruthenocene (RcCO) was investigated. Antibacterial activity in different media, growth inhibition, and killing kinetics of the most active peptides were determined. The toxicity of selected derivatives was determined against erythrocytes and three human cancer cell lines. It was shown that the replacement of an N-terminal arginine residue with a metallocenoyl moiety modulates the activity of WRWRW-peptides against Gram-positive and Gram-negative bacteria. MIC values of 2–6 µM for RcCO-W(RW)2 and 1–11 µM for (RW)3 were determined. Interestingly, W(RW)2-peptides derivatized with ferrocene were significantly less active than those derivatized with ruthenocene which have similar structural but different electronic properties, suggesting a major influence of the latter. The high activities observed for the RcCO-W(RW)2- and (RW)3-peptides led to an investigation of the origin of activity of these peptides using several important activity-related parameters. Firstly, killing kinetics of the RcCO-W(RW)2-peptide versus killing kinetics of the (RW)3 derivative showed faster reduction of the colony forming units for the RcCO-W(RW)2-peptide, although MIC values indicated higher activity for the (RW)3-peptide. This was confirmed by growth inhibition studies. Secondly, hemolysis studies revealed that both peptides did not lead to significant destruction of erythrocytes, even up to 500 µg/mL for (RW)3 and 250 µg/mL for RcCO-W(RW)2. In addition, toxicity against three human cancer cell lines (HepG2, HT29, MCF7) showed that the (RW)3-peptide had an IC50 value of ~140 µM and the RcW(RW)2 one of ~90 µM, indicating a potentially interesting therapeutic window. Both the killing kinetics and growth inhibition studies presented in this work point to a membrane-based mode of action for these two peptides, each having different kinetic parameters.
publisher	Beilstein-Institut
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511009/
_version_	1611936837134188544

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

Similar Items