Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond
Abstract
:1. Introduction—Drug Discovery in Venoms
2. Venom-Derived Peptides
2.1. Snake Venoms
2.2. Spider Venoms
2.3. Scorpion Venoms
2.4. Wasp Venoms
2.5. Venom-Derived Peptides in the Clinic
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptide | AA | Sequence | Peptide Family | Structure | Activity | Organism Producer | Reference |
---|---|---|---|---|---|---|---|
Snake Venom-Derived Peptides | |||||||
Crotamine | 42 | YKQCHKKGGHCFPKEKICLPPSSDFGKMDCRWRWKCCKKGSG | β-defensin-like | β1αβ2β3 N-terminal 𝛼-helix, two stranded antiparallel β-sheets, and two β-turns. | Antifungal (MIC = 12.5–50.0 μg mL−1) Anticancer activity (5 μg mL−1) | Crotalus durissus terrificus | [25,34] |
Crotalicidine | 34 | KRFKKFFKKVKKSVKKRLKKIFKKPMVIGVTIPF | Cathelicidin | α-helix at the N-terminal and random coil conformation at the C-terminal of the peptide. | Antibacterial (MIC < 10 μmol L−1), Anticancer (IC50 < 5 μmol L−1), Immunomodulatory activities | Crotalus durissus terrificus | [27,35] |
Spider Venom-Derived Peptides | |||||||
PnTx1 | 78 | AELTSCFPVGHECDGDASNCNCCGDDVYCGCGWGRWNCKCKVADQSYSYGICKDKVNCPNRHLWPAKVCKKCRRNCGG | ICK peptide | Disulfide bridge pattern | LD50 = 5.5 pmol g−1 (mice) Target: Nav channels, antagonist | Phoneutria nigriventer | [36,37] |
PnTx2-1 | 53 | ATCAGQDKPCKETCDCCGERGECVCALSYEGKYRCICRQGNFLIAWHKLASCK | ICK peptide | n.e. | Lethal in mice model at 0.02 pmol g−1 | Phoneutria nigriventer | [36,37] |
PnTx2-5 | 48 | ATCAGQDQTCKVTCDCCGERGECVCGGPCICRQGNFLIAWYKLASCKK | ICK peptide | n.e. | Lethal in mice model at 2.4 pmol g−1 | Phoneutria nigriventer | [36,37] |
PnTx2-6 | 48 | ATCAGQDQPCKETCDCCGERGECVCGGPCICRQGYFWIAWYKLANCKK | ICK peptide | n.e. | Lethal in mice model at 7.5 pmol g−1 | Phoneutria nigriventer | [36,37] |
PnTx2-9 | 32 | SFCIPFKPCKSDENCCKKFKCKTTGIVKLCRW | ICK peptide | n.e. | - | Phoneutria nigriventer | [36,37] |
PnTx3-1 | 41 | AECAAVYERCGKGYKRCCEERPCKCNIVMDNCTCKKFISEL | ICK peptide | n.e. | Paralysis in mice at 0.07 pmol g−1 Target: agonist of K+ channels | Phoneutria nigriventer | [36,37] |
PnTx3-2 | 46 | ACAGLYKKCGKGASPCCEDRPCKCDLAMGNCICKKKFIEFFGGGK | ICK peptide | n.e. | Antagonist of L-type CaV channels. Paralysis in mice 0.08 pmol g−1 | Phoneutria nigriventer | [36,37] |
PnTx3-3 | 34 | GCANAYKSCNGPHTCCWGYNGYLLACICSGXNWK | ICK peptide | n.e. | Lethal to mice at 0.07 pmol g−1 Antagonist of L-, P/Q- and R-type Cav channels | Phoneutria nigriventer | [36,37] |
PnTx3-4 | 77 | SCINVGDFCDGKKDDCQCCRDNAFCSCSVIFGYKTNCRCEVGTTATSYGICMAKHKCGRQTTCTKPCLSKRCKKNHG | ICK peptide | n.e. | Lethal to mice at 5 μg/mouse Target: antagonist of N-, P/Q- and R-type Cav channels | Phoneutria nigriventer | [36,37] |
PnTx3-5 | 45 | GCIGRNESCKFDRHGCCWPWSCSCWNKEGQPESDVWCECSLKIGK | ICK peptide | n.e. | Paralysis in mice 0.07 pmol g−1 Target: L-type Cav channels | Phoneutria nigriventer | [36,37] |
PnTx3-6 | 54 | ACIPRGEICTDDCECCGCDNQCYCPPGSSLGIFKCSCAHANKYFCNRKKEKCKK | ICK peptide | n.e. | Paralysis in mice 0.05 pmol g−1 Target: N-, P/Q- and L-type Cav channels | Phoneutria nigriventer | [36,37] |
PnTx4-3 | 48 | CGDINAACKEDCDCCGYTTACDCYWSSSCKCREAAIVIYTAPKKKLTC | ICK peptide | n.e. | Non-toxic to mice (288.5 pmol g−1) LD50 = 192.3 pmol g−1 (house fly) | Phoneutria nigriventer | [36,37] |
PnTx4 (5-5) | 47 | CADINGACKSDCDCCGDSVTCDCYWSDSCKCRESNFKIGMAIRKKF-C | ICK peptide | n.e. | Non-toxic to mice (290 pmol g−1) Target: NMDAR (antagonist), NaV channels (agonist) | Phoneutria nigriventer | [36,37] |
PnTx4 (6-1) | 48 | CGDINAACKEDCDCCGYTTACDCYWSKSCKCREAAIVIYTAPKKKLTC | ICK peptide | n.e. | LD50=9.3 ng/house fly Non-toxic to mice (286.2 pmol g−1) ED50= 36.3 pmol g−1 (house fly) Target: agonist NaV channels | Phoneutria nigriventer | [36,37] |
Psalmotoxin 1 (PcTX1) | 40 | EDCIPKWKGCVNRHGDCCEGLECWKRRRSFEVCVPKTPKT | ICK peptide | Three antiparallel ®-sheet structure with three disulfide bridges tightly folded into the “knottin” fold pattern | Antinociceptive effects IC50 = 36 pmol L−1 in glioma cells. | Psalmopoeuscambridgei | [38,39] |
U1-SCRTX-Lg1a | 16 | VGTDFSGNDDISDVQK | Anionic antimicrobial peptide (AAMP) | Random coil conformation with a <-helix structure between the ISDV residues | Active against Gram-negative bacteria (MIC 1.5–4.6 μmol L−1) | Loxoscelesgaucho | [40] |
Scorpion Venom-Derived Peptides | |||||||
Ts1 | 61 | KEGYLMDHEGCKLSCFIRPSGYCGRECGIKKGSSGYCAWPACYCYGLPNWVKVWDRATNKC | ®-like neurotoxin | Three antiparallel β-strands and a α-helix bonded by disulfide bridges | Toxic against mammals and insects Intravenous LD50 = 76 ± 9 μg kg−1 Target: Na+ channels | Tityus serrulatus | [41] |
Ts2 | 62 | KEGYAMDHEGCKFSCFIRPAGFCDGYCKTHLKASSGYCAWPACYCYGVPDHIKVWDYATNKC | ®-like neurotoxin | three β-strands and one α-helix, and is arranged in a triangular shape forming a cysteine-stabilized α-helix/ β-sheet (CSab) motif. three β-strands and one α-helix, and is arranged in a triangular shape forming a cysteine-stabilized α-helix/ β-sheet (CSab) motif. three β-strands and one α-helix, and is arranged in a triangular shape forming a cysteine-stabilized α-helix/ β-sheet (CSab) motif three β-strands and one α-helix, and is arranged in a triangular shape forming a cysteine-stabilized α-helix/β-sheet (CSab) motif Cysteine-stabilized α-helix/β-sheet (CSαβ) motif composed of three β-strands and one α-helix arranged in a triangular shape | Induction of inflammation and production of cytokines Inhibition of the rapid inactivation of some NaV channels | Tityus serrulatus | [41,42,43] |
Ts3 | 62 | KKDGYPVEYDNCAYICWNYDNAYCDKLCKDKKADSGYCYWVHILCYCYGLPDSEPTKTNGKC | α-neurotoxin | α-helix and three-stranded antiparallel β-sheet | Inhibition of the inactivation of NaV channels Muscle relaxation | Tityus serrulatus | [41,44] |
Ts5 | 64 | KKDGYPVEGDNCAFACFGYDNAYCDKLCKDKKADDGYCVWSPDCYCYGLPEHILKEPTKTSGRC | α-neurotoxin | Core composed of three β-strands and one α-helix | LD50 = 94 ± 7 μg kg−1 in mice Causes hypertension Target: Na+ channels | Tityus serrulatus | [41,45] |
Ts6 | 40 | WCSTCLDLACGASRECYDPCFKAFGRAHGKCMNNKCRCYT | α-KTx (Potassium channel toxin) | α-helix and triple-stranded β-sheet stabilized by four disulfide bridges | Induction of inflammation and production of cytokines Blockage of KV channels | Tityus serrulatus | [41,43] |
Ts7 | 37 | VFINAKCRGSPECLPKCKEAIGKAAGKCMNGKCKCYP | α-KTx (Potassium channel toxin) | n.e. | Blockage of K+ current Blockage of 86Rb efflux | Tityus serrulatus | [41] |
Ts8 | 60 | KLVALIPNDQLRSILKAVVHKVAKTQFGCPAYEGYCNDHCNDIERKDGECHGFKCKCAKD | ®-KTx (Potassium channel toxin) | n.e. | Blockage of voltage-gated non-inactivating K+ channels from rat brain synaptosomes at IC50: 30 nmol L−1 | Tityus serrulatus | [41] |
Ts9 | 35 | VVIGQRCYRSPDCYSACKKLVGKATGKCTNGRCDC | κ-KTx (Kappa potassium channel toxin) | Core composed of a short <-helix and a three-stranded antiparallel ®-sheet | Ligand for small-conductance apamin-sensitive calcium-activated potassium channel | Tityus serrulatus | [41] |
Wasp Venom-Derived Peptides | |||||||
Polybia-MPI | 14 | IDWKKLLDAAKQIL | Mastoparan | 71.43% α-helix | Antifungal activity (ED50 = 8–16 μmol L−1 Antimicrobial activity against Gram-positive and Gram-negative bacteria (MIC = 4–15 μg mL−1 | Polybiapaulista | [46,47] |
Polybia-MPII | 14 | INWLKLGKMVIDAL | Mastoparan | α-helix | Antimicrobial activity against Gram-positive bacteria (MIC = 2–5 μmol L−1 Antifungal activity (ED50 = 111–12.9 μmol L−1 Hemolytic properties (ED50 of 5 × 10 -5 mol L−1 | Pseudopolybiavespiceps Testacea, Polybia paulista | [46] |
Polybia-CP | 12 | ILGTILGLLKSL | Chemotactic peptide | 50% random coil 50% ambiguous conformations | Antimicrobial activity against Gram-positive bacteria (MIC = 15 μg mL−1 Mast cell degranulation (10−5 mol L−1) Low hemolytic activity | Polybiapaulista | [47] |
Peptide | Producer Organism | Description | Target | Target Indication | Company (Brand) | Clinical Trial | Reference |
---|---|---|---|---|---|---|---|
Captopril | Bothropsjararaca | Synthetic peptide based on bradykinin-potentiating peptides (BPP) | Angiotensin-converting enzyme (ACE) | Hypertension, cardiac failure | Bristol-Myers Squibb. (Capoten®) | Completed | [2,72,73,74,89] |
Enalapril | Bothropsjararaca | Synthetic peptide based on bradykinin-potentiating peptides (BPP) | Angiotensin-converting enzyme (ACE) | hypertension and cardiac failure | Merck (Vasotec®) | Completed | [72,75,76,89] |
Batroxobin | Brazilian lancehead snake (Bothrops moojeni) | Peptide isolated from venom | Cleavage of the Aα chain of fibrinogen at the [Ala]16-[Gly]17 bond | Defibrinogenating effect Anticoagulation therapy (thrombotic diseases) Diagnosis of fibrinogen levels and blood coagulation capabilities | Tobishi Pharmaceutical (Batroxobin, Reptilase, Defibrase) DSM Nutritional Products Ltd/Branch Pentapharm (Defibrase) Hanlim (Botropase) Juggat Pharma (Botropase, Botroclot) Drugs.com, (Botroclot) Plateltex S.R.O. (Plateltex-Act®) Vivostat A/S (Vivostat System). | Phase IV (Combination with anticoagulation in cerebral venous sinus thrombosis, NCT04269954) Completed in different countries | [72,77,78,79,90] |
Psalmotoxin 1 (PcTx-1) | Psalmopoeuscambridgei | Peptide isolated from venom | Inhibitor of AISCs | Pain treatment | - | Preclinical | [72,80,81] |
JNJ63955918 | Thrixopelmapruriens | Synthetic peptide based on the natural peptide ProTX-II | NaV1.7 channels | Pain treatment | Janssen | Preclinical | [2,81,82] |
GpTx-1 | Grammostila porter, Grammostila rosea, and Paraphysa scrofa | Peptide isolated from the venom | NaV1.7 channels | Pain treatment | Amgen | Preclinical | [2,81,83,84,85] |
[Ala5, Phe6, Leu26, Arg28]GpTx-1 | Grammostila porter, Grammostila rosea, and Paraphysa scrofa | Synthetic peptide based on the natural peptide GpTx-1 | NaV1.7, NaV1.5 and NaV1.4 channels | Pain treatment | Amgen | Preclinical | [2,81,83,84,85] |
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Ageitos, L.; Torres, M.D.T.; de la Fuente-Nunez, C. Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond. Int. J. Mol. Sci. 2022, 23, 15437. https://doi.org/10.3390/ijms232315437
Ageitos L, Torres MDT, de la Fuente-Nunez C. Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond. International Journal of Molecular Sciences. 2022; 23(23):15437. https://doi.org/10.3390/ijms232315437
Chicago/Turabian StyleAgeitos, Lucía, Marcelo D. T. Torres, and Cesar de la Fuente-Nunez. 2022. "Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond" International Journal of Molecular Sciences 23, no. 23: 15437. https://doi.org/10.3390/ijms232315437