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AMPs Review Article


Recent Antimicrobial Peptide (AMP) Product Citations


Common AMP Structural Motifs



The heavy use of traditional antibiotics over the past five decades has contributed to the growing numbers of antibiotic resistant strains of bacteria. According to European Centre for Disease Prevention and Control Antimicrobial Resistance Interactive Database (EARS-NET) in 2013, antimicrobial-resistant infections take a staggering toll of over 50,000 lives each year in the U.S. and Europe alone.[1] As an alternative, antimicrobial peptides (AMPs) are produced naturally by variety of organisms such as plants, amphibians, and mammals and are less susceptible to antibiotic resistance.

Often referred to as multifunctional molecules, AMPs provide a broad range of antibacterial activity, including acting as membrane disruptors,[2] effector molecules to intracellular proteins,[3–5] immunomodulators,[6] as well as in human contraception.[7,8] The broad modes of activity are due, in part, to the broad ranges of charge distributions and structural motifs that exist in AMPs (alpha-helices, beta-sheets, loops, and extended structures).[9–11]

In bacteria, AMP’s function by disrupting the cellular membranes or by translocating across membranes without disruption to target cellular organelles and intracellular proteins. Disruption of bacteria cell membranes begins with electrostatic interactions between the membrane and AMP. Following this electrostatic interaction, hydrogen-bonds form between basic amino acid residues in the peptide, lysine and arginine, and phosphate groups exposed on the membrane surface. This action causes the breakdown of salt bridges between the phosphate groups and neighboring cations to begin the process of membrane destabilization. In addition to the electrostatic interactions, hydrophobic interactions between uncharged residues (leucine, isoleucine, valine, tryptophan, and phenylalanine) and hydrophobic carbon chains of the Lipopolysaccharides (LPS) which further disrupt the close packing structure of the membrane causing more disorganization. Through a process known as “membrane thinning,”[12–13] when a critical concentration of AMPs is reached around the bacterium, the membrane becomes thin causing lateral expansions and increasing water translocation across the membrane. This disruption causes the membrane to leak and reduce membrane potentials leading to cell death.

Unlike membrane thinning, the introduction of membrane pores by AMPs results in the bacteria’s intracellular components to be quickly expelled causing rapid cell death.[14] The type of pore formed is affected by the structure of the AMP and can be generally described by either a barrel-stave or toroidal model. In the barrel-stave model, AMPs aggregate and then insert into the membrane bilayer so that hydrophobic regions (i.e., hydrophobic amino acid residues) of the peptide associate and align with the hydrocarbon core of the lipids through a process known as ‘hydrophobic matching’.[15] The hydrophilic regions of the AMP form the interior surface of the pore allowing hydrophilic molecules of appropriate size to move through freely.

In the toroidal pore model, AMPs penetrate deeper into the membrane and have less hydrophobic interactions than in the barrel-stave model. As a result of the electrostatic interactions with the polar head groups in the lipid bilayer, AMP’s pull the charged head groups into the bilayer causing membrane curvature and packing disruption. LL-37, melittin, and magainin are good examples of AMPs that induce toroidal pores with the latter forming 2 to 3 nm diameter-sized pores that only allow water-sized molecules to leak out. Pore-forming AMPs, including defensins, melittin, magainins, and LL-37 have been of particular interest for clinical development.

Article References:

  1. European Centre for Disease Prevention and Control Antimicrobial Resistance Interactive Database (EARS-NET) data for 2013.
  2. Shai, Yechiel. Peptide Science 66.4 (2002): 236-248.
  3. Hancock, Robert EW. The Lancet Infectious Diseases 1.3 (2001): 156-164.
  4. Risso, Angela. Journal of Leukocyte Biology 68.6 (2000): 785-792.
  5. Nicolas, Pierre. The FEBS Journal 276.22 (2009): 6483-6496.
  6. Mansour, Sarah C., Olga M. Pena, and Robert EW Hancock. Trends in Immunology 35.9 (2014): 443-450.
  7. Yedery, R. D., and K. V. R. Reddy. The European Journal of Contraception & Reproductive Health Care 10.1 (2005): 32-42.
  8. Srakaew, Nopparat, et al. Human Reproduction 29.4 (2014): 683-696.
  9. Dathe, Margitta, and Torsten Wieprecht. Biochimica et Biophysica Acta (BBA)-Biomembranes 1462.1 (1999): 71-87.
  10. Selsted, Michael E., et al. Journal of Biological Chemistry 268.9 (1993): 6641-6648.
  11. Bulet, Phillipe, et al. Developmental & Comparative Immunology 23.4 (1999): 329-344.
  12. Sato, Hiromi, and Jimmy B. Feix. Biochimica et Biophysica Acta (BBA)-Biomembranes 1758.9 (2006): 1245-1256.
  13. Gottler, Lindsey M., and Ayyalusamy Ramamoorthy. Biochimica et Biophysica Acta (BBA)-Biomembranes 1788.8 (2009): 1680-1686.
  14. Brogden, Kim A. Nature Reviews. Microbiology 3.3 (2005): 238.
  15. Harroun, Thad A., et al. Biophysical Journal 76.2 (1999): 937-945.

Table 1. Common antimicrobial peptide secondary structures and mechanisms of activity. Click on the peptide names to learn more.


Histatin 5 

DSHAKRHHGYKRKFHEKHHSHRGY M.Nishikata et al., Biochem. Biophys. Res. Commun., 174, 625 (1991) Histidine-Rich ROS generation



(a) G.H. Gudmundsson et al.,Eur. J. Biochem., 238, 325 (1996); (b) Madera, Laurence, and Robert EW Hancock. Journal of Innate Immunity 4.5-6 (2012): 553-568; (c) Choi, Ka€Yee G., Scott Napper, and Neeloffer Mookherjee. Immunology 143.1 (2014): 68-80. a-Helix Toroidal pore, carpet

Cecropin B


D. Andreau et al., PNAS, 80, 6475 (1983) a-Helix Channel formation

Cecropin A, porcine


D. Andreu et al., Proc. 20th Euro. Pept. Symp., 361 (1988) a-Helix Channel formation

Cecropin P1, porcine


J.Y. Lee et al., PNAS, 86, 9159 (1989) a-Helix Channel formation



C. Subbalakshmi et al., FEBS Letters, 395, 48 (1996) Tryptophan-rich, extended Pore

Defensin-1 (human) HNP-1

(3 disulfide bridges)

M.E. Selsted et al., J. Clin. Invest., 76, 1436 (1985) b-Sheet Pore, carpet

beta-Defensin-2, human

(3 disulfide bridges)

Schröder, Jens-M., and Jürgen Harder. "Human beta-defensin-2." The International Journal of Biochemistry & Cell Biology 31.6 (1999): 645-651. b-Sheet Pore, carpet

alpha-Defensin 6

(3 disulfide bridges)

P.A.Raj et al., Biochem. J., 347, 633 (2000) b-Sheet Pore, carpet

Defensin HNP-3 (human)

(3 disulfide bridges)

P.A.Raj et al., Biochem. J., 347, 633 (2000) b-Sheet Pore, carpet

Defensin (human) HNP-2

(3 disulfide bridges)

Selsted, M. and S. Harwig, J. Biol. Chem. 264, 4003 (1989) b-Sheet Pore, carpet

beta-Defensin-1, human

(3 disulfide bridges)

Hoover, David M., Oleg Chertov, and Jacek Lubkowski. "The Structure of Human β-Defensin-1 NEW INSIGHTS INTO STRUCTURAL PROPERTIES OF β-DEFENSINS." Journal of Biological Chemistry 276.42 (2001): 39021-39026. b-Sheet, a-helix Pore, carpet

beta-Defensin-4, human

(3 disulfide bridges)

García, José-Ramón Conejo, et al. "Human β-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity." The FASEB Journal 15.10 (2001): 1819-1821. b-Sheet, a-helix Pore, carpet

beta-Defensin-3, human

(3 disulfide bridges)

(a) J. Harder, J. Bartels, E. Christophers, and J.-M. Schröder, J. Biol. Chem., 276, 5707 (2001) (Original); (b) L.A. Duits, et al., Biochem. Biophys. Res. Commun., 280, 522 (2001); (c) H.P. Jia, et al., Gene, 263, 211 (2001). b-Sheet, a-helix Pore, carpet



A. Mor et al., Biochemistry, 30, 8824 (1991) a-helix Toroidal pore



Raynor et al., J. Biol. Chem., 266, 2753 (1991); Schweitz, Toxicon, 22, 308 (1984)

a-helix in membrane

Toroidal pore/carpet, ROS generation