Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted Cα amino acids

Hicks, Rickey P.

doi:10.1016/j.bmc.2016.06.048

Cited by 27 publications

(16 citation statements)

References 61 publications

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“…Both strategies take into consideration the improvement of the physicochemical properties, like amphipathicity, hydrophobicity, and overall positive charge, with the objective of better activity toward the target cells (Huang et al, 2011 ; Melo et al, 2011 ; Sinthuvanich et al, 2012 ). Furthermore, other strategies such as hybridizing different ACPs (Hoskin and Ramamoorthy, 2008 ) or changing the amino acids used for unnatural ones (D-enantiomers or cyclic tetra-substitution of C α are examples; Hicks, 2016 ) have also been tested. The possibilities are endless, and depend on what the focus of the improvement is for each case.…”

Section: Peptides With Antimicrobial and Anticancer Activitymentioning

confidence: 99%

Peptides with Dual Antimicrobial and Anticancer Activities

et al. 2017

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In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

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Section: Peptides With Antimicrobial and Anticancer Activitymentioning

confidence: 99%

Peptides with Dual Antimicrobial and Anticancer Activities

et al. 2017

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“…Clearly, the prospects are as big as the challenges. Recent reviews highlight the strong pharmaceutical potential of ncAA-supplemented drugs against various pathogens, e.g., MRSA, Acinetobacter baumannii , C. difficile , and Pseudomonas aeruginosa ( Blaskovich, 2016 ; Hicks, 2016 ; Wang et al, 2016 ; Baumann et al, 2017 ). The modification of AMPs with new-to-nature ncAAs presents a versatile tool to fight the increasing lack of antimicrobial drugs ( Blaskovich, 2016 ; Baumann et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Expanding the Genetic Code of Lactococcus lactis and Escherichia coli to Incorporate Non-canonical Amino Acids for Production of Modified Lantibiotics

et al. 2018

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The incorporation of non-canonical amino acids (ncAAs) into ribosomally synthesized and post-translationally modified peptides, e.g., nisin from the Gram-positive bacterium Lactococcus lactis, bears great potential to expand the chemical space of various antimicrobials. The ncAA Nε-Boc-L-lysine (BocK) was chosen for incorporation into nisin using the archaeal pyrrolysyl-tRNA synthetase–tRNAPyl pair to establish orthogonal translation in L. lactis for read-through of in-frame amber stop codons. In parallel, recombinant nisin production and orthogonal translation were combined in Escherichia coli cells. Both organisms synthesized bioactive nisin(BocK) variants. Screening of a nisin amber codon library revealed suitable sites for ncAA incorporation and two variants displayed high antimicrobial activity. Orthogonal translation in E. coli and L. lactis presents a promising tool to create new-to-nature nisin derivatives.

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“…Compared with natural amino acids, non-natural amino acids have three main advantages: (i) they have a variety of physiochemical properties [ 80 ]; (ii) non-natural amino acids provide greater control of the conformational flexibility of the peptides, thus increasing the potential for organism selectivity and potency [ 81 ]; and (iii) they have higher metabolic stability [ 79 ]. Researchers have synthesized a new set of short peptides with the use of tetrahydroisoquinoline carboxylic acid (Tic) instead of phenylalanine, octahydroindolecarboxylic acid (Oic) instead of proline, 1-aminocyclohexane carboxylic acid (A6c)/A5c instead of alanine or leunine and 2,4-diaminobutanoic acid/2,4-diaminopropionic acid instead of lysine to transform the template peptide; the experimental results showed that the modified A6c-Gly-Tic/Oic had 15 times higher anti-tumour activity, the IC 50 value in 12 types of cancer cells was less than 7.5 µM, and it was non-toxic to normal cells [ 66 ]. Another non-natural amino acid used in ACPs modification is d -amino acid.…”

Section: Reconstruction and Modification Of Acpmentioning

confidence: 99%

Anti-cancer peptides: classification, mechanism of action, reconstruction and modification

2020

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Anti-cancer peptides (ACPs) are a series of short peptides composed of 10–60 amino acids that can inhibit tumour cell proliferation or migration, or suppress the formation of tumour blood vessels, and are less likely to cause drug resistance. The aforementioned merits make ACPs the most promising anti-cancer candidate. However, ACPs may be degraded by proteases, or result in cytotoxicity in many cases. To overcome these drawbacks, a plethora of research has focused on reconstruction or modification of ACPs to improve their anti-cancer activity, while reducing their cytotoxicity. The modification of ACPs mainly includes main chain reconstruction and side chain modification. After summarizing the classification and mechanism of action of ACPs, this paper focuses on recent development and progress about their reconstruction and modification. The information collected here may provide some ideas for further research on ACPs, in particular their modification.

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Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted Cα amino acids

Cited by 27 publications

References 61 publications

Peptides with Dual Antimicrobial and Anticancer Activities

Peptides with Dual Antimicrobial and Anticancer Activities

Expanding the Genetic Code of Lactococcus lactis and Escherichia coli to Incorporate Non-canonical Amino Acids for Production of Modified Lantibiotics

Anti-cancer peptides: classification, mechanism of action, reconstruction and modification

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