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Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids
(1) Background: (KLAKLAK)(2) is a representative of the antimicrobial peptide group which also shows good anticancer properties. (2) Methods: Herein, we report synthesis using SPPS and characterization by HPLC/MS of a series of shortened analogues of (KLAKLAK)(2). They contain single sequence KLAKLA...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915940/ https://www.ncbi.nlm.nih.gov/pubmed/33567789 http://dx.doi.org/10.3390/molecules26040898 |
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author | Jaber, Sirine Iliev, Ivan Angelova, Tsvetelina Nemska, Veronica Sulikovska, Inna Naydenova, Emilia Georgieva, Nelly Givechev, Ivan Grabchev, Ivo Danalev, Dancho |
author_facet | Jaber, Sirine Iliev, Ivan Angelova, Tsvetelina Nemska, Veronica Sulikovska, Inna Naydenova, Emilia Georgieva, Nelly Givechev, Ivan Grabchev, Ivo Danalev, Dancho |
author_sort | Jaber, Sirine |
collection | PubMed |
description | (1) Background: (KLAKLAK)(2) is a representative of the antimicrobial peptide group which also shows good anticancer properties. (2) Methods: Herein, we report synthesis using SPPS and characterization by HPLC/MS of a series of shortened analogues of (KLAKLAK)(2). They contain single sequence KLAKLAK as C-terminal amides. In addition, substitution of some natural amino acids with unnatural β-Ala and nor-Leu is realized. In addition, these structures are conjugated with second pharmacophore with well proven anticancer properties 1,8-naphthalimide or caffeic acid. Cytotoxicity, antiproliferative effect and antimicrobial activity of newly synthesized structures were studied. (3) Results: The obtained experimental results reveal significant selective index for substances with common chemical structure KLβAKLβAK-NH(2). The antibacterial properties of newly synthesized analogues at two different concentrations 10 μM and 20 μM, were tested against Gram-negative microorganisms Escherichia coli K12 407. Only two of the studied compounds KLAKLAK-NH(2) and the one conjugated with second pharmacophore 1,8-naphthalimide and unnatural amino acid nor-Leu showed moderate activity against tested strains at concentration of 20 μM. (4) Conclusions: The obtained results reveal that the introducing of 1,8-naphthalimideGly- and Caf- increase the cytotoxicity and antiproliferative activity of the peptides but not their selectivity. Only two compounds KLAKLAK-NH(2) and 1,8-naphthalimideGKnLAKnLAK-NH(2) show moderate activity against Escherichia coli K12 at low concentration of 20 μM. |
format | Online Article Text |
id | pubmed-7915940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79159402021-03-01 Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids Jaber, Sirine Iliev, Ivan Angelova, Tsvetelina Nemska, Veronica Sulikovska, Inna Naydenova, Emilia Georgieva, Nelly Givechev, Ivan Grabchev, Ivo Danalev, Dancho Molecules Article (1) Background: (KLAKLAK)(2) is a representative of the antimicrobial peptide group which also shows good anticancer properties. (2) Methods: Herein, we report synthesis using SPPS and characterization by HPLC/MS of a series of shortened analogues of (KLAKLAK)(2). They contain single sequence KLAKLAK as C-terminal amides. In addition, substitution of some natural amino acids with unnatural β-Ala and nor-Leu is realized. In addition, these structures are conjugated with second pharmacophore with well proven anticancer properties 1,8-naphthalimide or caffeic acid. Cytotoxicity, antiproliferative effect and antimicrobial activity of newly synthesized structures were studied. (3) Results: The obtained experimental results reveal significant selective index for substances with common chemical structure KLβAKLβAK-NH(2). The antibacterial properties of newly synthesized analogues at two different concentrations 10 μM and 20 μM, were tested against Gram-negative microorganisms Escherichia coli K12 407. Only two of the studied compounds KLAKLAK-NH(2) and the one conjugated with second pharmacophore 1,8-naphthalimide and unnatural amino acid nor-Leu showed moderate activity against tested strains at concentration of 20 μM. (4) Conclusions: The obtained results reveal that the introducing of 1,8-naphthalimideGly- and Caf- increase the cytotoxicity and antiproliferative activity of the peptides but not their selectivity. Only two compounds KLAKLAK-NH(2) and 1,8-naphthalimideGKnLAKnLAK-NH(2) show moderate activity against Escherichia coli K12 at low concentration of 20 μM. MDPI 2021-02-08 /pmc/articles/PMC7915940/ /pubmed/33567789 http://dx.doi.org/10.3390/molecules26040898 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jaber, Sirine Iliev, Ivan Angelova, Tsvetelina Nemska, Veronica Sulikovska, Inna Naydenova, Emilia Georgieva, Nelly Givechev, Ivan Grabchev, Ivo Danalev, Dancho Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids |
title | Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids |
title_full | Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids |
title_fullStr | Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids |
title_full_unstemmed | Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids |
title_short | Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)(2)-NH(2) and Their Conjugates Containing Unnatural Amino Acids |
title_sort | synthesis, antitumor and antibacterial studies of new shortened analogues of (klaklak)(2)-nh(2) and their conjugates containing unnatural amino acids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915940/ https://www.ncbi.nlm.nih.gov/pubmed/33567789 http://dx.doi.org/10.3390/molecules26040898 |
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