Synthesis, antitumor and antibacterial studies of new shortened analogues of (KLAKLAK)2-NH2 and their conjugates containing unnatural amino acids
creativework.keywords | (KLAKLAK)2-NH2, 1, 8-naphthalimide, Anticancer peptides, Anticancer properties, Antimicrobial activity, Caffeic acid, Unnatural amino acids | |
creativework.publisher | MDPI AG | en |
dc.contributor.author | Jaber S. | |
dc.contributor.author | Iliev I. | |
dc.contributor.author | Angelova T. | |
dc.contributor.author | Nemska V. | |
dc.contributor.author | Sulikovska I. | |
dc.contributor.author | Naydenova E. | |
dc.contributor.author | Georgieva N. | |
dc.contributor.author | Givechev I. | |
dc.contributor.author | Grabchev I. | |
dc.contributor.author | Danalev D. | |
dc.date.accessioned | 2024-07-10T14:27:04Z | |
dc.date.accessioned | 2024-07-10T14:49:37Z | |
dc.date.available | 2024-07-10T14:27:04Z | |
dc.date.available | 2024-07-10T14:49:37Z | |
dc.date.issued | 2021-02-02 | |
dc.description.abstract | (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-NH2. 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-NH2 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-naphthalimideGlyand Caf- increase the cytotoxicity and antiproliferative activity of the peptides but not their selectivity. Only two compounds KLAKLAK-NH2 and 1,8-naphthalimideGKnLAKnLAK-NH2 show moderate activity against Escherichia coli K12 at low concentration of 20 μM. | |
dc.identifier.doi | 10.3390/molecules26040898 | |
dc.identifier.issn | 1420-3049 | |
dc.identifier.scopus | SCOPUS_ID:85101452121 | en |
dc.identifier.uri | https://rlib.uctm.edu/handle/123456789/624 | |
dc.language.iso | en | |
dc.source.uri | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101452121&origin=inward | |
dc.title | Synthesis, antitumor and antibacterial studies of new shortened analogues of (KLAKLAK)2-NH2 and their conjugates containing unnatural amino acids | |
dc.type | Article | |
oaire.citation.issue | 4 | |
oaire.citation.volume | 26 |