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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...

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Autores principales: Jaber, Sirine, Iliev, Ivan, Angelova, Tsvetelina, Nemska, Veronica, Sulikovska, Inna, Naydenova, Emilia, Georgieva, Nelly, Givechev, Ivan, Grabchev, Ivo, Danalev, Dancho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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