Table 1.

Selected examples of targeted AMPs generated using rational design, computational design, or high-throughput screening

Peptide(s)	Type/characteristics	Discovery/design methodology	Target	Reference
cCF10-C4	Hybrid AMP	Fusion (by a GGG linker) of Enterococcus faecalis–specific peptide pheromone cCF10 to C4, a broad-spectrum AMP modified to have a lower positive charge	E. faecalis; at least eightfold less active on Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhimurium, Salmonella pullorum, Escherichia coli	24
Peptide 13	STAMP, hybrid AMP	Fusion of weakly targeting AMP to targeting AMP previously discovered through phage display; peptides were modified with charged residues at the N or C terminus to alter physicochemical properties	E. coli; at least eightfold less active on Staphylococcus, Pseudomonas, Lactobacillus strains	75
C16G2	STAMP	Fusion of two peptides: killing and targeting moieties; targeting domain is a bacterial pheromone; killing domain is derived from broad-spectrum AMP novispirin G10	Streptococcus mutans in the oral microbiota	22, 23
RI16-T9W	Amphipathic, helical	Point mutation (T9W) to RI16, a fragment sequence of the cathelicidin PMAP-36; rational design to disrupt sites important for amphipathicity	Pseudomonas aeruginosa	26
Peptide 3	Peptide fusion	Fusion of acetyltransferase inhibitor peptide to cell penetrating peptide; targets lipid A biosynthesis	Order of magnitude decrease in MICs for panel of gram-negative bacteria; twofold increase in MIC for S. aureus	28
Guavanin 2	Arginine rich, α-helical	Genetic algorithm optimization of a guava peptide; ratio between hydrophobic moment and α-helix propensity was used in fitness function	Selective toward gram-negative species: E. coli, Acinetobacter baumannii (6.25 μM MIC); less active against S. aureus, Streptococcus pyogenes, Listeria ivanovii, E. faecalis (≥50 μM MIC)	34
SP1, SP2, SP3, SP4	Short, charged	DBAASP prediction algorithm based on clustering of 9 peptide physiochemical features; modified AMPs included D-enantiomers	Designed to target gram-negative bacteria; varying activities toward E. coli, P. aeruginosa, A. baumannii, Enterococcus cloacae, Klebsiella pneumoniae (≤0.125 – ≥32 μg/ml MIC); not tested on gram-positive bacteria	37
NN2_0018, NN2_0022, NN2_0024, NN2_0027, NN2_0029, NN2_0035, NN2_0039, NN2_0046, NN2_0050, NN2_0055	Short, charged	LSTM language model trained on MIC data against E. coli; top 10 sequences synthesized and characterized	Designed to target E. coli; varying activities (0.25 – ≥ 128 μg/ml MIC) toward 30 different gram-positive and gram-negative cultures	38
PA2-GNU7	Hybrid AMP, helical	Phage display high-throughput screening and conjugation to GNU7, a broad-spectrum AMP with a GGG linker; the peptides individually or combined separately were less effective than the conjugated peptide	Selectively active on P. aeruginosa in mixed cultures with either E. coli or S. typhimurium	58
Peptides P1–P18	Random sequence	Bacterial high-throughput self-screening of surface displayed peptide libraries	Varying activities toward E. coli, P. aeruginosa, A. baumannii (≤2 – >128 μM MIC)	48
KAM5, KAM8	Disulfide-cyclized	Phage display high-throughput screening of peptides containing 2-acetylphenylboronic acid moieties	KAM5: S. aureus, no binding to E. coli or Bacillus subtilis; KAM8: A. baumannii, no binding to E. coli or S. aureus	49
Apidaecin and its analogs	Short, proline-rich	Alanine substitution screening; peptides synthesized using SPOT synthesis	Single amino acid substitutions to apidaecin resulted in varying activities toward P. aeruginosa, E. coli, S. aureus (0.63 – >125 μg/ml MIC)	44

Abbreviations: AMP, antimicrobial peptide; CSP, competence-stimulating peptide; DBAASP, Database of Antimicrobial Activity and Structure of Peptides; LSTM, long short-term memory; MIC, minimum inhibitory concentration; STAMP, specifically targeted antimicrobial peptide.