Table 2.
Summary of different strategies in translating the therapeutic potentials of host defense peptides (HDPs).
| Methods | HDPs template | Strategies | Biological effects |
|---|---|---|---|
| Residue substitution | |||
| Lee et al. (40) | HP ribosomal protein 1 | Pro substitution | Increased antimicrobial efficacy |
| Wang et al. (86) | LL-37 | Ala/Val substitution | Increased antimicrobial efficacy |
| Blondelle et al. (37) | Melittin | Trp substitution | Reduced host tissue toxicity |
| Hybridization | |||
| Wei et al. (117) | Cecropin and LL-37 | Hybridization | Increased antimicrobial efficacy and reduced host tissue toxicity |
| Wu et al. (118) | Melittin and LL-37 | Hybridization | Increased antimicrobial efficacy and reduced host tissue toxicity |
| Boman et al. (112) | Cecropin and melittin | Hybridization | Improved antimicrobial efficacy and reduced host tissue toxicity |
| Unnatural AA | |||
| Arias et al. (101) | Indolicidin | Ornithine, DAB, DAP, Agb, and hArg | Improved antimicrobial activity against GN and proteolytic stability |
| Clemens et al. (100) | Cecropin and magainin | Ornithine | Good antimicrobial and anti-biofilm efficacies against GP and GN |
| Hicks et al. (103) | Magainin | Tic-Oic | Increased antimicrobial activity against GP, GN and mycobacterium and reduced host tissue toxicity |
| L-to-D isomerization | |||
| Jia et al. (131) | Polybia-CP | LDI | Improved proteolytic stability and reduced host tissue toxicity |
| Manabe et al. (132) | Sapesin B | LDI | Improved antimicrobial efficacy against GP, GN and fungi |
| Carmona et al. (130) | Pandinin 2 | LDI | Reduced host tissue toxicity |
| C- and N- terminal modifications | |||
| Saikia et al. (139) | MreB | N-acetylation | Improved antimicrobial efficacy in salt |
| Falciani et al. (148) | M33 | C-pegylation | Increased proteolytic stability |
| Dennison and Phoenix (143) | Modelin-5 | C-amidation | Improved stabilization of alpha-helix and antimicrobial efficacy |
| Cyclization | |||
| Mwangi et al. (161) | Cathelicidin-BF | Cyclization | Increased antimicrobial and antibiofilm efficacies against MDR-GN and good proteolytic stability |
| Scudiero et al. (160) | HBD-1 and−3 | Cyclization | Increased proteolytic stability |
| Fernandez-Lopez et al. (154) | De novo | Cyclization of D,L-alpha peptides | Increased antimicrobial efficacy |
| Incorporation with nanoparticles | |||
| Comune et al. (171) | LL-37 | Gold NP | Improved wound healing |
| Casciaro et al. (176) | Esculentin-1a | Gold NP | Improved antimicrobial efficacy, wound healing, and proteolytic stability |
| Chereddy et al. (169) | LL-37 | PLGA NP | Improved wound healing |
| Smart design with artificial intelligence technology | |||
| Yount et al. (184) | 5,200 12-mer peptide sequence | SVM-based classifier | Identification of a unifying alpha-core signature of peptide with good correlation with ability to generate NGC |
| Lee et al. (183) | 572 alpha-helical peptides | SVM-based classifier | Accurate prediction of peptide ability to generate NGC |
| Cherkasov et al. (182) | Random 9-mer peptide database | QSAR model using ANN | Generation of highly active synthetic peptides against MDR GP and GN, with low toxicity |
Three representative examples are provided for each strategy, in order of chronology.
HP, Helicobacter pylori; GP, Gram-positive bacteria; GN, Gram-negative bacteria; DAB, 2,4-diamino-butyric acid; DAP, 2,3-diamino-propionic acid (DAP); Agb, (S)-2-amino-4-guanidinobutyric acid; hArg, homo-arginine; Tic-Oic, tetrahydroisoquionolinecarboxylic acid-octahydroindolecarboxylic acid dipeptide; HBD, Human-beta-defensin; PLGA, Poly lactic-co-glycolic acid; SVM, support vector machine; NGC, Negative Gaussian curvature; ANN, Artificial neural network; MDR, Multidrug resistant.