Antimicrobial peptides (AMPs), originally referring to a class of alkaline peptides with antimicrobial activity induced in insects, have a molecular weight of approximately 2000-7000 and consist of 20-60 amino acid residues. Most of these active peptides are characterized by strong alkalinity, thermal stability, and broad-spectrum antimicrobial properties.
The first antimicrobial peptide discovered in the world was Cecropins, which was identified in 1980 by Swedish scientist G. Boman and others. It is an antimicrobial peptide produced by pupae of Hyalophora cecropia induced by injection of Serratia marcescens and Escherichia coli. Initially, during the study on the immune mechanism of the North American silkworm, it was found that antimicrobial peptides, named Cecropins, were produced in the hemolymph of its diapausing pupae after induction by external stimuli. Later, structurally similar antimicrobial peptides were isolated from other insects, as well as amphibians and mammals, with over 70 types of their structures determined.
In the years after 1980, people successively discovered and isolated antimicrobial active polypeptides from bacteria, fungi, amphibians, insects, higher plants, mammals, and even humans. Due to their broad-spectrum and high-efficiency bactericidal activity, they were named "antibacterial peptides (ABP)". With the deepening of research, it was found that some antibacterial peptides have strong killing effects on certain fungi, protozoa, viruses, and cancer cells. Therefore, many scholars tend to name such active polypeptides "peptide antibiotics". In addition, natural antimicrobial peptides have selective immune activation and regulatory functions, and exhibit good preventive and protective effects against sepsis.
(a) α-helix (b) β-strand
(c) β-hairpin or loop (d) extended
Classification
Structural: Antimicrobial peptides are mainly categorized into Cathelicidin and Defensin, with 5 types:
(1) α-helical peptides (no cysteine) or two α-helical segments linked by random coils;
(2) Peptides rich in specific amino acids (no cysteine);
(3) Peptides with one disulfide bond;
(4) Peptides with two+ disulfide bonds and β-sheet structure;
(5) Antimicrobial peptides derived from larger functional peptides.
Cecropins (first isolated) and Magainins (from African clawed frogs) belong to type 1 (Cecropin-like), extensively studied.
Source-based: 6 categories:
(1) Insect-derived (numerous due to largest population);
(2) Mammalian (e.g., Cecropin P1 from porcine intestine, 1989);
(3) Amphibian (skin secretions with ancient defensive peptides);
(4) From fish, mollusks, crustaceans;
(5) Plant defensins (similar to insect/mammalian ones);
(6) Bacteriocins (from Gram-positive/negative bacteria, including cationic/neutral peptides).
Functions: Broad-spectrum antimicrobial activity, rapid target elimination. Many are natural, showing potential as therapeutics against Gram-negative/positive bacteria, fungi, parasites, tumor cells.
Effects: Strong bactericidal action, especially against drug-resistant pathogens. Some kill viruses, fungi, protozoa, cancer cells; may enhance immunity and accelerate wound healing, promising medical applications.
Physicochemical properties:
Natural antimicrobial peptides are small basic peptides (30+ amino acids, ~4000 Daltons) with good water solubility, thermostability (retaining activity at 100°C for 10-15min), cationic properties (pI >7), and resistance to extreme ionic strength, pH, and some proteases. They have selective immune-modulating functions, protecting against sepsis—a life-threatening bacterial infection causing systemic inflammation, organ failure, and high mortality via excessive pro-inflammatory cytokines. Amid antibiotic resistance issues, natural antimicrobial peptides offer promise for new therapeutics, though research focuses mainly on direct bactericidal effects. Reptilian cathelicidin peptides and derivatives selectively activate innate immunity in sepsis models (including drug-resistant strains) via p38 MAPK pathway, stimulating anti-inflammatory cytokines and chemokines without excessive harmful inflammation, providing effective sepsis prevention and protection.
Application Prospects:
Antimicrobial peptides hold broad pharmaceutical potential due to their high activity, broad spectrum, diversity, and low risk of inducing bacterial resistance. Most clinical trials currently focus on topical treatments, which are safe and effective—evidenced by more toxic peptides/lipopeptides like gramicidin S and polymyxin B used in skin ointments. In agriculture, their genes are engineered to develop disease-resistant crops, with promising results against potato bacterial wilt, tobacco bacterial wilt, and rice bacterial blight. They show no harm to normal mammalian cells but can kill cancer cell lines and some viruses. Additionally, certain peptide antibiotics, active against plant pathogenic bacteria and fungi, are applied in plant disease-resistant genetic engineering.