Effects of Substituting Arginine by Lysine in Bovine Lactoferricin Derived Peptides: Pursuing Production Lower Costs, Lower Hemolysis, and Sustained Antimicrobial Activity

Cárdenas-Martínez, Karen Johanna; Grueso-Mariaca, Derly; Vargas-Casanova, Yerly; Bonilla-Velásquez, Laura; Estupiñán, Sandra Mónica; Parra-Giraldo, Claudia Marcela; Leal, Aura Lucía; Rivera‐Monroy, Zuly Jenny; García‐Castañeda, Javier Eduardo

doi:10.1007/s10989-021-10207-x

Cited by 6 publications

(13 citation statements)

References 67 publications

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“…On the other hand, the substitution of all Arg residues with Lys in chimera C7 did not increase the antifungal activity (MIC 200 µg/mL, 101 µM). Moreover, the results reported for C5 and C6 are similar to those obtained by Pineda et al: C5 (MIC 100 µg/Ml, 48 µM) and C6 (MIC 50 µg/mL,24 µM) showed greater antibacterial activity than chimera C2 (MIC 200 µg/mL,122 µM) [ 18 , 33 ]. According to the above, although for chimera C5 and C7 the MIC values can be considered similar to those of the precursors (controls), the C6 chimera exhibited greater activity, obtaining a MIC value up to 4 times lower than RRWQWR and RLLRRLLR peptides.…”

Section: Resultssupporting

confidence: 85%

Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

et al. 2022

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Antimicrobial peptides (AMPs) are considered to be a valuable source for the identification and/or design of promising candidates for the development of antifungal treatments, since they have advantages such as lower tendency to induce resistance, ease of production, and high purity and safety. Bovine lactoferricin (LfcinB) and buforin II (BFII) are AMPs to which great antimicrobial potential has been attributed. The minimum motives with antimicrobial activity derived from LfcinB and BFII are RRWQWR and RLLR, respectively. Nine chimeras containing the minimum motives of both peptides were synthesized and their antifungal activity against fluconazole (FLC)-sensitive and resistant C. albicans, C. glabrata, and C. auris strains was evaluated. The results showed that peptides C9: (RRWQWR)2K-Ahx-RLLRRRLLR and C6: KKWQWK-Ahx-RLLRRLLR exhibited the greatest antifungal activity against two strains of C. albicans, a FLC-sensitive reference strain and a FLC-resistant clinical isolate; no medically significant results were observed with the other chimeras evaluated (MIC ~200 µg/mL). The chimera C6 was also active against sensitive and resistant strains of C. glabrata and C. auris. The combination of branched polyvalent chimeras together with FLC showed a synergistic effect against C. albicans. In addition to exhibiting antifungal activity against reference strains and clinical isolates of Candida spp., they also showed antibacterial activity against both Gram-positive and Gram-negative bacteria, suggesting that these chimeras exhibit a broad antimicrobial spectrum and can be considered to be promising molecules for therapeutic applications.

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Section: Resultssupporting

confidence: 85%

Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

et al. 2022

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“…They showed that chimeras with partial substitution of Arg with Lys maintained antimicrobial activity. In addition, it has been proven that the partial substitution of amino acids favors peptide synthesis and reduces costs [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The designed and synthesized peptides used for the purpose of this study were: C5: RRWQWR-Ahx-KLLKKLLK, C6: KKWQWK-Ahx-RLLRRLLR, and precursor peptides LfcinB (20)(21)(22)(23)(24)(25): RRWQWR, BFII (32)(33)(34)(35) Pal : RLLRRLLR, [K]-LfcinB (20)(21)(22)(23)(24)(25): KKWQWK, and [K]-BFII (32)(33)(34)(35) Pal : KLLKKLLK [18,19]. In both chimeras, 6-aminohexanoic acid (Ahx) was used as the spacer molecule.…”

Section: Antifungal Activity Of Chimeric Peptides Derived From Bovine...mentioning

confidence: 99%

“…Mutants exposed to the C5 chimera exhibited a MIC between ≤3.125 and 12.5 µg/mL; when the mutants were incubated with the C6 chimera, they exhibited a MIC of 3.125 to 6.25 µg/mL. On the other hand, when treating the mutants with the precursor peptides of LfcinB (20)(21)(22)(23)(24)(25) and BFII (32)(33)(34)(35) Pal , the MIC was >25 and >50 µg/mL, respectively (Table 2).…”

Section: Antifungal Activity Of Chimeric Peptides Derived From Bovine...mentioning

confidence: 99%

“…In light of the above, the present study evaluated the in vitro antifungal activity of chimeric peptides containing LfcinB (20)(21)(22)(23)(24)(25): RRWQWR and BFII (32)(33)(34)(35): RLLR sequences; specifically, the effect of chimeras on C. neoformans var. grubii strains.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

et al. 2022

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Cryptococcosis is associated with high rates of morbidity and mortality. The limited number of antifungal agents, their toxicity, and the difficulty of these molecules in crossing the blood–brain barrier have made the exploration of new therapeutic candidates against Cryptococcus neoformans a priority task. To optimize the antimicrobial functionality and improve the physicochemical properties of AMPs, chemical strategies include combinations of peptide fragments into one. This study aimed to evaluate the binding of the minimum activity motif of bovine lactoferricin (LfcinB) and buforin II (BFII) against C. neoformans var. grubii. The antifungal activity against these chimeras was evaluated against (i) the reference strain H99, (ii) three Colombian clinical strains, and (iii) eleven mutant strains, with the aim of evaluating the possible antifungal target. We found high activity against these strains, with a MIC between 6.25 and 12.5 µg/mL. Studies were carried out to evaluate the effect of the combination of fluconazole treatments, finding a synergistic effect. Finally, when fibroblast cells were treated with 12.5 µg/mL of the chimeras, a viability of more than 65% was found. The results obtained in this study identify these chimeras as potential antifungal molecules for future therapeutic applications against cryptococcosis.

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Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

et al. 2023

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Breast cancer is one of the main causes of premature death in women; current treatments have low selectivity, generating strong physical and psychological sequelae. The palindromic peptide R-1-R (RWQWRWQWR) has cytotoxic activity against different cell lines derived from cancer and selectivity against noncancerous cells. To determine if changes in the charge/length of this peptide increase its activity, six peptides were obtained by SPPS, three of them with addition of Arg at the N, C-terminal or both and three with deletion of Arg at the N, C-terminal or both. The cytotoxic and selective activities were evaluated against MCF-7, MDA-MB-231, and MCF-12 cell lines and fibroblast primary cell culture, evidencing that the RR-1-R peptide with the inclusion of Arg in the N-terminal end maintained selectivity and increased cytotoxicity against lines derived from breast cancer. The effect of this addition regarding the type of induced cell death was evaluated by flow cytometry, showing very low rates of necrosis and a significant majority of apoptotic events with activation of both Caspase 8 and Caspase 9. This work allowed us to find a modification that generates a peptide with greater cytotoxic effects and can be considered a promising molecule for other approaches to improve anticancer peptides.

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Effects of Substituting Arginine by Lysine in Bovine Lactoferricin Derived Peptides: Pursuing Production Lower Costs, Lower Hemolysis, and Sustained Antimicrobial Activity

Cited by 6 publications

References 67 publications

Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

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