Host-defense peptides of the skin with therapeutic potential: From hagfish to human

Conlon, J. Michael

doi:10.1016/j.peptides.2015.03.005

Cited by 26 publications

(21 citation statements)

References 135 publications

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“…Such skin secretions constitute the amphibians' first line of defense, consisting of their innate immunity. The secretions produced by the anuran skin granular glands have been screened for many biological activities, including antimicrobial, antineoplastic, antiviral, contraceptive and anthelminthic activities [67,68].…”

Section: Anuran Skin Peptidesmentioning

confidence: 99%

Antiviral activity of animal venom peptides and related compounds

Mata

Mourão

Rangel

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.

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Section: Anuran Skin Peptidesmentioning

confidence: 99%

Antiviral activity of animal venom peptides and related compounds

Mata

Mourão

Rangel

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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“…The side-chains of three Cys at positions 3, 4 and 10 in a modified [D-Phe 7 ]-α-MSH [3][4][5][6][7][8][9][10][11][12][13] sequence together with an amino group can form an NS 3 -type chelating structure after appropriate folding of the peptide. As a consequence of the complexation with the radiometal, the initially linear MSH peptide will be cyclized [101].…”

Section: Chelators For Radiometals Used In Melanoma Targetingmentioning

confidence: 99%

“…The former chelator yielded superior biodistribution results than the latter. Incorporation of 99m Tc(N)](Cys-Ahx-β-Ala)} containing cyclic MSH [4][5][6][7][8][9][10][11][12][13] analog [108]. The stability of the latter radiopeptide complex in vivo was judged good; however non-specific tissue uptake of 99m Tc was relatively high and thus the potential of the peptide limited.…”

Section: Chelators For Radiometals Used In Melanoma Targetingmentioning

confidence: 99%

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Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Eberlé

Rout

et al. 2017

CMC

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Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions. Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides.

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“…Amino peptides (AMPs) represent an evolutionary very ancient (>500 MY BP) immunological defence against microbes (Beisswenger and Bals, 2005;Pushpanathan et al, 2013) and are produced by all Metazoa, including cnidaria (Bosch, 2013), protozoa, insects, amphibians and mammals (Conlon, 2015;Pasupuleti et al, 2012) as well as by plants (Salas et al, 2015). AMPs belong to a unique and diverse group of molecules that are divided into subgroups on the basis of their amino acid composition, structure and mode of action (Yount and Yeaman, 2006).…”

Section: Introductionmentioning

confidence: 99%

Design and expression of peptides with antimicrobial activity againstSalmonellatyphimurium

Porta

Petrone

Morello

et al. 2016

Cellular Microbiology

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We showed previously that insertion of Synechocystis Δ -desaturase in salmonella's membrane alters membrane physical state (MPS), followed by the expression of stress genes causing inability to survive within murine macrophages (MΦ). Recently, we showed that expression of one membrane lipid domain (MLD) of Δ -desaturase (ORF200) interferes with salmonella MPS, causing loss of virulence in mice and immunoprotection. Here, we postulate that an α-antimicrobial peptide (α-AMP) intercalates within membrane lipids, and depending on its amino acid sequence, it does so within specific key sensors of MLD. In this study, we choose as target for a putative synthetic AMP, PhoP/PhoQ, a sensor that responds to low Mg concentration. We synthesised a modified DNA fragment coding for an amino acid sequence (NUF) similar to that fragment and expressed it in salmonella typhimurium. We showed that the pattern of gene expression controlled by PhoP/PhoQ highlights dysregulation of pathways involving phospholipids biosynthesis, stress proteins and genes coding for antigens. RNA-Seq of strain expressing ORF200 showed that the pattern of those genes is also altered here. Accumulation of NUF conferred temporary immunoprotection. This represents a powerful procedure to address synthetic α-AMPs to a specific MLD generating live non-virulent bacterial strains.

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Host-defense peptides of the skin with therapeutic potential: From hagfish to human

Cited by 26 publications

References 135 publications

Antiviral activity of animal venom peptides and related compounds

Antiviral activity of animal venom peptides and related compounds

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Design and expression of peptides with antimicrobial activity againstSalmonellatyphimurium

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