Cargando…

Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes

As the technologies for peptide synthesis and development continue to mature, antimicrobial peptides (AMPs) are being widely studied as significant contributors in medicinal chemistry research. Furthermore, the advancement in the synthesis of dendrimers’ design makes dendrimers wonderful nanostructu...

Descripción completa

Detalles Bibliográficos
Autores principales: Khan, Arif Iftikhar, Nazir, Shahzad, Ullah, Aaqib, Haque, Muhammad Nadeem ul, Maharjan, Rukesh, Simjee, Shabana U., Olleik, Hamza, Courvoisier-Dezord, Elise, Maresca, Marc, Shaheen, Farzana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221442/
https://www.ncbi.nlm.nih.gov/pubmed/35740895
http://dx.doi.org/10.3390/biom12060770
_version_ 1784732623504932864
author Khan, Arif Iftikhar
Nazir, Shahzad
Ullah, Aaqib
Haque, Muhammad Nadeem ul
Maharjan, Rukesh
Simjee, Shabana U.
Olleik, Hamza
Courvoisier-Dezord, Elise
Maresca, Marc
Shaheen, Farzana
author_facet Khan, Arif Iftikhar
Nazir, Shahzad
Ullah, Aaqib
Haque, Muhammad Nadeem ul
Maharjan, Rukesh
Simjee, Shabana U.
Olleik, Hamza
Courvoisier-Dezord, Elise
Maresca, Marc
Shaheen, Farzana
author_sort Khan, Arif Iftikhar
collection PubMed
description As the technologies for peptide synthesis and development continue to mature, antimicrobial peptides (AMPs) are being widely studied as significant contributors in medicinal chemistry research. Furthermore, the advancement in the synthesis of dendrimers’ design makes dendrimers wonderful nanostructures with distinguishing properties. This study foregrounds a temporin SHa analog, [G10a]-SHa, and its dendrimers as globular macromolecules possessing anticancer and antibacterial activities. These architectures of temporin SHa, named as [G10a]-SHa, its dendrimeric analogs [G10a](2)-SHa and [G10a](3)-SHa, and [G10a](2)-SHa conjugated with a polymer molecule, i.e., Jeff-[G10a](2)-SHa, were synthesized, purified on RP-HPLC and UPLC and fully characterized by mass, NMR spectroscopic techniques, circular dichroism, ultraviolet, infrared, dynamic light scattering, and atomic force microscopic studies. In pH- and temperature-dependent studies, all of the peptide dendrimers were found to be stable in the temperature range up to 40–60 °C and pH values in the range of 6–12. Biological-activity studies showed these peptide dendrimers possessed improved antibacterial activity against different strains of both Gram-positive and Gram-negative strains. Together, these dendrimers also possessed potent selective antiproliferative activity against human cancer cells originating from different organs (breast, lung, prostate, pancreas, and liver). The high hemolytic activity of [G10a](2)-SHa and [G10a](3)-SHa dendrimers, however, limits their use for topical treatment, such as in the case of skin infection. On the contrary, the antibacterial and anticancer activities of Jeff-[G10a](2)-SHa, associated with its low hemolytic action, make it potentially suitable for systemic treatment.
format Online
Article
Text
id pubmed-9221442
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92214422022-06-24 Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes Khan, Arif Iftikhar Nazir, Shahzad Ullah, Aaqib Haque, Muhammad Nadeem ul Maharjan, Rukesh Simjee, Shabana U. Olleik, Hamza Courvoisier-Dezord, Elise Maresca, Marc Shaheen, Farzana Biomolecules Article As the technologies for peptide synthesis and development continue to mature, antimicrobial peptides (AMPs) are being widely studied as significant contributors in medicinal chemistry research. Furthermore, the advancement in the synthesis of dendrimers’ design makes dendrimers wonderful nanostructures with distinguishing properties. This study foregrounds a temporin SHa analog, [G10a]-SHa, and its dendrimers as globular macromolecules possessing anticancer and antibacterial activities. These architectures of temporin SHa, named as [G10a]-SHa, its dendrimeric analogs [G10a](2)-SHa and [G10a](3)-SHa, and [G10a](2)-SHa conjugated with a polymer molecule, i.e., Jeff-[G10a](2)-SHa, were synthesized, purified on RP-HPLC and UPLC and fully characterized by mass, NMR spectroscopic techniques, circular dichroism, ultraviolet, infrared, dynamic light scattering, and atomic force microscopic studies. In pH- and temperature-dependent studies, all of the peptide dendrimers were found to be stable in the temperature range up to 40–60 °C and pH values in the range of 6–12. Biological-activity studies showed these peptide dendrimers possessed improved antibacterial activity against different strains of both Gram-positive and Gram-negative strains. Together, these dendrimers also possessed potent selective antiproliferative activity against human cancer cells originating from different organs (breast, lung, prostate, pancreas, and liver). The high hemolytic activity of [G10a](2)-SHa and [G10a](3)-SHa dendrimers, however, limits their use for topical treatment, such as in the case of skin infection. On the contrary, the antibacterial and anticancer activities of Jeff-[G10a](2)-SHa, associated with its low hemolytic action, make it potentially suitable for systemic treatment. MDPI 2022-05-31 /pmc/articles/PMC9221442/ /pubmed/35740895 http://dx.doi.org/10.3390/biom12060770 Text en © 2022 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
Khan, Arif Iftikhar
Nazir, Shahzad
Ullah, Aaqib
Haque, Muhammad Nadeem ul
Maharjan, Rukesh
Simjee, Shabana U.
Olleik, Hamza
Courvoisier-Dezord, Elise
Maresca, Marc
Shaheen, Farzana
Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes
title Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes
title_full Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes
title_fullStr Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes
title_full_unstemmed Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes
title_short Design, Synthesis and Characterization of [G10a]-Temporin SHa Dendrimers as Dual Inhibitors of Cancer and Pathogenic Microbes
title_sort design, synthesis and characterization of [g10a]-temporin sha dendrimers as dual inhibitors of cancer and pathogenic microbes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221442/
https://www.ncbi.nlm.nih.gov/pubmed/35740895
http://dx.doi.org/10.3390/biom12060770
work_keys_str_mv AT khanarififtikhar designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT nazirshahzad designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT ullahaaqib designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT haquemuhammadnadeemul designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT maharjanrukesh designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT simjeeshabanau designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT olleikhamza designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT courvoisierdezordelise designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT marescamarc designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes
AT shaheenfarzana designsynthesisandcharacterizationofg10atemporinshadendrimersasdualinhibitorsofcancerandpathogenicmicrobes