Cecropin | Encyclopeptide

Chemical Identity

Cecropin A (from H. cecropia)

Property	Value
Name	Cecropin A
Source	Hyalophora cecropia (giant silk moth) hemolymph
Sequence	`KWKLFKKIGAVLKVLTTGLPALIS`
Length	37 amino acids
Chemical Formula	C₂₀₄H₃₄₉N₄₉O₃₉
Molecular Weight	4487.3 Da
Net Charge	+6 at neutral pH
Hydrophobicity	Amphipathic (α-helical)
PDB Structure	2K0G (NMR in DPC micelles)

Other Cecropin Family Members

Cecropin	Source	Sequence	MW
Cecropin A	H. cecropia	KWKLFKKIGAVLKVLTTGLPALIS	4487
Cecropin B	H. cecropia	KWKVFKKIGAVLKVLTTGLPALIS	4471
Cecropin D	Sarcophaga peregrina	DFWGILQSIGKALTGALKTILGTL	2779
Cecropin P1	Porcine intestine	SWLSKTAKKLENSAKKRISEGIAIAIQGGPR	3325

Discovery

Cecropins were the first antibacterial peptides isolated from insects, discovered by Boman and colleagues in 1981 from the hemolymph of the giant silk moth Hyalophora cecropia after immune challenge.

Structure

Cecropins are linear, cationic peptides (net charge +4 to +6) that adopt an amphipathic α-helical structure in membrane environments:

N-terminal region (1-11): Hydrophobic, inserts into lipid bilayers
C-terminal region (12-37): More polar, faces aqueous phase
Helix break: Proline residue at position 12 creates a kink, separating two helical segments

Structural Features

Feature	Detail
Structure type	Amphipathic α-helix
Hydrophobic moment	High (0.74)
Critical micelle concentration	~5 μM
Optimal activity	pH 5.5-7.5

Mechanism of Action

Cecropins kill bacteria through membrane disruption:

Electrostatic binding: Cationic peptide binds anionic bacterial membrane
Insertion: Hydrophobic face inserts into lipid bilayer
Pore formation: Creates voltage-dependent ion channels (1-2 nS conductance)
Lysis: Membrane depolarization → cell death

Membrane Selectivity

Target	Activity	IC50
E. coli	++	0.5-2 μM
S. aureus	+	2-10 μM
P. aeruginosa	++	0.3-1 μM
Human erythrocytes	-	>100 μM

Biosynthesis

Cecropins are synthesized as preprocecropins:

Signal peptide (21 aa) → secreted
Propeptide (8 aa) → cleaved
Mature cecropin (25-37 aa) → active

Therapeutic Potential

Advantages

Broad-spectrum activity (Gram-negative > Gram-positive)
Rapid killing (minutes)
Low resistance development
Anti-biofilm activity
Immunomodulatory effects

Challenges

Susceptibility to proteolytic degradation
Hemolytic activity at high concentrations
Short in vivo half-life
Cost of synthesis

Drug Development

Strategy	Example	Status
D-amino acid substitution	cecropin A analogs	Research
Cyclization	head-to-tail cecropin A	Research
PEGylation	cecropin A-PEG	Research
Nanoparticle encapsulation	cecropin A-liposome	Preclinical
Hybrid peptides	cecropin-melittin hybrid	Research

Research Applications

Antibiotic resistance: Model for developing novel antibiotics
Cancer therapy: Cecropin A has selective anticancer activity
Wound healing: Antimicrobial + anti-inflammatory properties
Gene therapy: Cecropin A gene delivery

References

Steiner H, et al. “Antibacterial immunity induced by a cecropin.” PNAS 78:7629-7633, 1981. doi:10.1073/pnas.78.12.7629
Boman HG. “Antibacterial peptides: key components of the innate immune system.” Cell 65:205-207, 1991. doi:10.1016/0092-8674(91)90153-T
Steiner H, et al. “Complete sequence of the blood lytic factor cecropin B.” Nature 319:184-186, 1986. doi:10.1038/319184a0
Boman HG. “Peptide antibiotics and their role in innate immunity.” Annual Review of Immunology 13:61-92, 1995. doi:10.1146/annurev.iy.13.040195.000421
Chelikani P, et al. “Design of cecropin-melittin hybrid peptides with enhanced antimicrobial activity.” Biochemical and Biophysical Research Communications 281:660-665, 2001.