What are antimicrobial peptides?


Antimicrobial peptides play an important role in the defense mechanisms of organisms. They also referred to as “host defense peptides” in higher eukaryotic organisms. Antimicrobial peptides are part of the innate immunity. Most of them consist of 5-40 amino acids with a molecular weight of less than 10kDa. They act as natural antibiotics and provide effective defense against infections. But some studies have shown new functions like antineoplastic effects, wound healing, skin regeneration and others. Due to increasing antimicrobial resistance, synthetic as well as natural antimicrobial peptides are interesting alternatives. Antimicrobial peptides interact primarily with microorganisms, showing no toxicity toward mammalian cells. They destroy microorganisms mostly by membrane disruption, making it difficult for microorganisms to develop resistance. Hence, acquired resistance did not become an issue with antimicrobial peptides.

Antimicrobial peptides are classified into four major groups:

Generally antimicrobial peptides carry hydrophobic residues and a net positive charge allowing to interact with the negatively charged cell membrane. This interaction with a bacterial membrane leads to leakage of cell contents. Eukaryotic antimicrobial peptides can be categorized into cationic ones: defensinscathelicidins,cecropins, thionins, amino acid enriched peptides, histones. There are also anionic neuropeptide-derived and aspartic acid-rich peptides. Proposed models for the mechanism of action are the “Barrel-Stave model”, the “Toroidal model” (“Wormhole model”) or the “Carpet model”.

The Barrel-Stave model describes a mechanism in which antimicrobial peptides form a barrel-like pore within the bacterial membrane with the individual antimicrobial peptides or their complexes being the staves. Arranged in this manner, the hydrophobic regions of the antimicrobial peptides point outwards towards the acyl chains of the membrane whereas the hydrophilic areas form the pore. This model is proposed e.g. for dermcidin. The pores described by the Toroidal Pore model differ from those of the Barrel-Stave model. Primarily, the outer and inner leaflets of the membrane are not intercalated in the transmembrane channel. This model is proposed for LL-37. A different mechanism is proposed in the Carpet model where antimicrobial peptides first cover the outer surface of the membrane and then disrupt the membrane like detergents by forming micelle-like units. Certain antimicrobial peptides penetrate the bacterial membrane without channel formation. They act on intracellular targets by e.g. inhibiting nucleic acid and/or protein synthesis. This model is proposed for piscidins.

Apart from therapeutic usage, research is also going to employing antimicrobial peptides as surface active molecules, e.g. attaching them to the surface of implantable medical devices to reduce biofilm formation. A challenge here is to reach sufficient surface concentrations of the peptides. Binding of antimicrobial peptides to a Silicon Foley catheter reduced the biofilm formation by pathogens causing urinary tract infection. For diagnostics purpose, synthetic antimicrobial peptides designed with highly specific targeting and binding capabilities were immobilized onto a microsensor array. This allowed rapid and multiplexed detection of bacterial pathogens. Linking antimicrobial peptides to nanoparticles leads to site specific targeting and delivery of drug molecules. Dermaseptin entrapped in chitosan nanoparticles has shown to be slightly more active against tumor cells than the free peptide.

Bachem also offers a large portfolio of antimicrobial peptides and related compounds (shop.www.bachem.com).


Bachem monograph Antimicrobial Peptides, 2008870 published by Global Marketing, Bachem Group (2016)
G. Wang et al., Antimicrobial peptides in 2014, Pharmaceuticals 8, 123-150 (2015)
J.P. da Costa et al., Antimicrobial peptides: an alternative for innovative medicines? Appl Microbiol Biotechnol 99, 2023-40 (2015)
B. E. Oyinloye, Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases, Pharmaceuticals 8, 151-175 (2015)


Drug resistant-bacteria are estimated to cause 25000 deaths and cost more than 1.5 billion USD each year in healthcare related expenses and productivity losses in the European Union alone (1). Hence, drug-resistant infections are a serious global health problem and there is an urgent need for novel antimicrobials. Antimicrobial peptides (AMPs) are of interest as potential therapeutics as broad-spectrum antibiotics for various microorganisms. AMPs have the ability to avoid antimicrobial resistance in many cases.

More than 5000 AMPs have been discovered or synthesized to date (2) and several companies have AMPs in various stages of active development, from preclinical studies to Phase III. A selection of AMPs in active clinical development is highlighted in Table 1 below.


Product NameActive IngredientCompanies InvolvedHighest PhaseCondition Treated
Locilex®pexiganan acetateAbeona Therapeutics Inc, SmithKline Beecham Plc,
RRD International LLC, GlaxoSmithKline plc,
Dipexium Pharmaceuticals Inc

IIIDiabetic Foot Ulcer(III)
Skin Infections(I)
CLS001omiganan pentahydrochlorideCadence Pharmaceuticals Inc, Fujisawa Pharmaceutical Co., Ltd., Cutanea Life Sciences, Biowest Therapeutics Inc.,
Maruho Co Ltd
 IIIPapulopustular Rosacea(III)
Acne Vulgaris(II)
Atopic Dermatitis(II)
MK4261surotomycinCubist Pharmaceuticals Inc,
Merck & Co Inc
 IIIClostridium Difficile Associated Diarrhea(III)
TD1792--Innoviva, Theravance Biopharma U.S Inc, R-Pharm IIISkin Bacterial Infections(III)
C16G2--UCLA School of Dentistry, Chengdu Sen Nuo Wei Biotechnology Co Ltd, C3 Jian Inc IIDental Caries(II)
DPK060--DermaGen AB, Pergamum AB IIAtopic Dermatitis(II)
Otitis Externa(II)
LL37--Pergamum AB IIVaricose Ulcer(II)
LytixarTMLTX109Lytix Biopharma AS IIImpetigo(II)
Staphylococcal Infections(II)
Novexatin®--NovaBiotics Ltd IITinea Unguium(II)
POL7080--Polyphor Ltd, Roche IIPseudomonas Infections(II)
Inimex Pharmaceuticals Inc, SciClone Pharmaceuticals Inc, Soligenix Inc
 IITherapy Induced Side-effects(II)
Bacterial Infections(I)
Immunology and Inflammation(PC)
Skin Bacterial Infections(PC)
Ulcerative Colitis(PC)
NVB302--Novacta Biosystems Limited IClostridium Difficile Infections(I)

Table 1: AMPs in Active Phase I to Phase III Development and Pending Approval (3), (4)

Phase III Clinical Candidates
Locilex® (pexiganan acetate) is a synthetic 22-amino acid peptide originally isolated from the skin of the African Clawed Frog. Locilex has demonstrated bactericidal activity against gram-positive, gram negative, aerobic, anerobic and resistant bacteria (4). This AMP acts by altering bacterial cell membrane permeability. Dipexium Pharmaceuticals is currently conducting two pivotal Phase III clinical trials of Locilex in mild diabetic foot ulcers and the company plans to file a New Drug Application (NDA) and Marketing Authorization Application (MAA) for Locilex in 2017 (5).

Cutanea Life Sciences is developing CLS001 (omiganan pentahydrochloride), an antibiotic and antimicrobial cationic peptide, for rosacea and other indications. In 2015, Cutanea Life Sciences initiated a Phase III study to evaluate the safety and efficacy of once-daily CLS001 topical gel versus vehicle administered in patients with papulopustual rosacea (3).

Cubist Pharmaceuticals, a subsidiary of Merck & Co, is developing MK4261 (surotomycin) for the treatment of Clostridium difficile associated diarrhea (CDAD). Surotomycin is a lipopeptide that exhibits potent and rapid bactericidal activity. In 2015, Cubist announced the completion of a Phase III study of surotomycin in patients with CDAD (3).

TD1792 is a synthetic glycopeptide-cephalosporin heterodimer which is designed to combine the antibacterial activities of its glycopeptide and beta-lactam components. Theravance Biopharma has partnered with R-Pharm to develop TD1792 as a treatment for infections caused by gram-positive infections. Theravance has completed a Phase II proof-of-concept study of TD1792 and R-Pharm has initiated a Phase III study of TD1792 in complicated skin and soft tissue infections caused by gram-positive bacteria (3).

The urgent need to develop new antimicrobials has been driving AMP research and clinical candidates forward. Further AMPs may enter clinical trials in the future as several preclinical candidates are in the pipeline. To support researchers and organizations working in the area of AMPs, Bachem offers a wide variety of AMP catalog peptides, comprehensive custom peptide synthesis services and production of peptide-based New Chemical Entities.
For further reading we recommend our AMP brochure, which is available for you as pdf download in our technical library here.


(1) World Health Organization. Antibiotic Resistance. World Health Organization. [Online] October 2015. [Cited: April 29, 2016.] http://www.who.int/mediacentre/factsheets/antibiotic-resistance/en/
(2) Bahar, AA and Ren D. Antimicrobial Peptides. Pharmaceuticals. Dec 2013, Vol. 6, 12, pp. 1543-1575.
(3) Medtrack. [Online] [Cited: May 2, 2016.]
(4) Locilex. Dipexium Pharmaceuticals. [Online] 2016. [Cited: May 6, 2016.] http://www.dipexiumpharmaceuticals.com/locilex/overview
(5) Dipexium Pharmaceuticals Reaches 75% Enrollment Milestone in Pivotal Phase 3 Clinical Trials. Dipexium Pharmaceuticals. [Online] February 4, 2016. [Cited: May 9, 2016.] http://ir.dipexiumpharmaceuticals.com/press-releases/detail/205/dipexium-pharmaceuticals-reaches-75-enrollment-milestone