Modification Strategy of D-leucine Residue Addition on a Novel Peptide from Odorrana schmackeri, with Enhanced Bioactivity and In Vivo Efficacy

Yao, Aifang; Ma, Yufei; Chen, Xiaoling; Xi, Xinping; Ma, Chengbang; Ren, Shengxiang; Shaw, Chris; Wang, Lei

doi:10.3390/toxins13090611

Cited by 5 publications

(7 citation statements)

References 62 publications

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“…The antimicrobial efficiency of temporin-PKE and its analogues against S. aureus (ATCC 6538) was conducted as described in a previous paper [ 31 ]. S. aureus in the logarithmic growth phase (OD = 0.23 at 550 nm) was diluted by MHB medium to obtain a final density of 5 × 10 5 CFU/mL.…”

Section: Methodsmentioning

confidence: 99%

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Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships

et al. 2022

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Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of Pelophylax kl. esculentus and it displays a strong activity against Gram-positive bacteria, with an extreme cytotoxicity. Incorporating positively charged residues and introducing D-amino acids were the two main strategies adopted for the modifications. The transformation of the chirality of Ile could reduce haemolytic activity, and an analogue with appropriate D-isoforms could maintain antimicrobial activity and stability. The substitution of hydrophobic residues could bring about more potent and broad-spectrum antimicrobial activities. The analogues with Lys were less harmful to the normal cells and their stabilities remained at similarly high levels compared to temporin-PKE. The optimal number of charges was three, and the replacement on the polar face was a better choice. Temporin-PKE-3K exerted dually efficient functions includingstrong antimicrobial and anticancer activity. This analogue showed a reduced possibility for inducing resistance in MRSA and Klebsiella pneumoniae, a rather strong antimicrobial activity in vivo, and it exhibited the highest therapeutic index such that temporin-PKE-3K has the potential to be developed as a clinical drug.

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Section: Methodsmentioning

confidence: 99%

“…The anti-proliferative activities of peptides against HCT-116, NCI-H838 (H838), U251MG, PC-3, and NCI-H157 cell lines were determined by MTT cell viability assay [ 31 ], and the details were described in Section 2.9 .…”

Section: Methodsmentioning

confidence: 99%

Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships

et al. 2022

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“…Interestingly, human non-small cell lung cancer cells cannot survive after 2 h of treatment with only 10 μM of d-leucine alone, significantly increasing the killing efficiency. Furthermore, this treatment showed low cytotoxicity to normal cells [ 32 ].…”

Section: Application Strategies Of Natural Anticancer Peptides and Pr...mentioning

confidence: 99%

Amphibian-Derived Natural Anticancer Peptides and Proteins: Mechanism of Action, Application Strategies, and Prospects

Chen,

Wu,

et al. 2023

IJMS

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Cancer is one of the major diseases that seriously threaten human life. Traditional anticancer therapies have achieved remarkable efficacy but have also some unavoidable side effects. Therefore, more and more research focuses on highly effective and less-toxic anticancer substances of natural origin. Amphibian skin is rich in active substances such as biogenic amines, alkaloids, alcohols, esters, peptides, and proteins, which play a role in various aspects such as anti-inflammatory, immunomodulatory, and anticancer functions, and are one of the critical sources of anticancer substances. Currently, a range of natural anticancer substances are known from various amphibians. This paper aims to review the physicochemical properties, anticancer mechanisms, and potential applications of these peptides and proteins to advance the identification and therapeutic use of natural anticancer agents.

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“…The peptides were chemically synthesised by a solid-phase peptide synthesiser (Tribute 2-channel peptide synthesiser, Protein Technologies, Tucson, AZ, USA). The whole synthesis process was described in detail in a previous paper [43]. The amino acids were weighed accurately and mixed with 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU).…”

Section: Synthesis Of R2aw and Its Five Designed Analoguesmentioning

confidence: 99%

“…In the MTT assay, [Lys 4,19 , Leu 20 ]R2AW(1-22)-NH 2 showed the best antiproliferative activity against human prostate cancer cells, PC-3. In this context, the cytotoxicity of [Lys 4,19 , Leu 20 ]R2AW(1-22)-NH 2 on PC-3 cells was determined by trypan blue exclusion assay [43]. Cells (2 × 10 5 cells/well) were seeded into a 12-well plate and incubated at 37 • C with 5% CO 2 overnight.…”

Section: Trypan Blue Exclusion Assaysmentioning

confidence: 99%

Progressive Design of a Ranatuerin-2 Peptide from Amolops wuyiensis: Enhancement of Bioactivity and In Vivo Efficacy

Yao,

Liu,

Cai

et al. 2023

Antibiotics

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Antimicrobial peptides (AMPs) that exert multiple functions are considered promising candidates to combat the bacterial drug resistance crisis. Nowadays, targeted peptide modification has been widely recognised to improve biological activity and make up for deficiencies in clinical applications such as toxicity. In this study, a helix-loop peptide was isolated and identified from the skin secretion of the Wuyi torrent frog Amolops wuyiensis, namely, ranatuerin-2-AW (R2AW) (GFMDTAKNVAKNVAATLLDKLKCKITGGC). Target modifications were made to R2AW to study the structure–activity relationships and to optimise its bioactivities. Five analogues were progressively designed via residue substitution and truncation and the antibacterial and anticancer activities were evaluated. We found that the serine-substitution and cyclic-domain-deletion products showed similar antibacterial activity to the natural peptide R2AW, implying that the disulphide bridge and Rana box were dispensable for the antibacterial activity of ranatuerin-2 peptides. Notably, the cationicity- and hydrophobicity-enhanced variant, [Lys4,19, Leu20]R2AW(1-22)-NH2, exhibited significantly optimised antibacterial and anticancer activities. Additionally, it killed bacteria by membrane disruption at a highly efficient rate. Moreover, [Lys4,19, Leu20]R2AW(1-22)-NH2 exerted potential in vivo efficacy in a methicillin-resistant Staphylococcus aureus (MRSA)-infected waxworm model. Overall, this study demonstrated some rational design ideas for optimising the dual antibacterial and anticancer activities of ranatuerin-2 peptides and it proposes [Lys4,19, Leu20]R2AW(1-22)-NH2 as an appealing candidate for therapeutic development.

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Modification Strategy of D-leucine Residue Addition on a Novel Peptide from Odorrana schmackeri, with Enhanced Bioactivity and In Vivo Efficacy

Cited by 5 publications

References 62 publications

Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships

Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships

Amphibian-Derived Natural Anticancer Peptides and Proteins: Mechanism of Action, Application Strategies, and Prospects

Progressive Design of a Ranatuerin-2 Peptide from Amolops wuyiensis: Enhancement of Bioactivity and In Vivo Efficacy

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