MEET US AT THE WEBINAR ON PEPTIDES IN ALZHEIMER’S RESEARCH
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: amphipathic α-helical (dermaseptin, LL-37), β-sheet (defensins), β-hairpin (bactenecin, tachyplesins) and extended antimicrobial peptides (indolicidin, histatins). 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: defensins, cathelicidins,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.
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 Name||Active Ingredient||Companies Involved||Highest Phase||Condition Treated|
|Locilex®||pexiganan acetate||Abeona Therapeutics Inc, SmithKline Beecham Plc,|
RRD International LLC, GlaxoSmithKline plc,
Dipexium Pharmaceuticals Inc
|III||Diabetic Foot Ulcer(III)|
|CLS001||omiganan pentahydrochloride||Cadence Pharmaceuticals Inc, Fujisawa Pharmaceutical Co., Ltd., Cutanea Life Sciences, Biowest Therapeutics Inc.,|
Maruho Co Ltd
|MK4261||surotomycin||Cubist Pharmaceuticals Inc,|
Merck & Co Inc
|III||Clostridium Difficile Associated Diarrhea(III)|
|TD1792||--||Innoviva, Theravance Biopharma U.S Inc, R-Pharm||III||Skin Bacterial Infections(III)|
|C16G2||--||UCLA School of Dentistry, Chengdu Sen Nuo Wei Biotechnology Co Ltd, C3 Jian Inc||II||Dental Caries(II)|
|DPK060||--||DermaGen AB, Pergamum AB||II||Atopic Dermatitis(II)|
|LL37||--||Pergamum AB||II||Varicose Ulcer(II)|
|LytixarTM||LTX109||Lytix Biopharma AS||II||Impetigo(II)|
|Novexatin®||--||NovaBiotics Ltd||II||Tinea Unguium(II)|
|POL7080||--||Polyphor Ltd, Roche||II||Pseudomonas Infections(II)|
Inimex Pharmaceuticals Inc, SciClone Pharmaceuticals Inc, Soligenix Inc
|II||Therapy Induced Side-effects(II)|
Immunology and Inflammation(PC)
Skin Bacterial Infections(PC)
|NVB302||--||Novacta Biosystems Limited||I||Clostridium Difficile Infections(I)|
What is your official job title at Bachem?
My official title is Technical Sales Manager.
How long have you been with Bachem?
I have worked at Bachem for one and a half year. I worked at Baxter Biosciences before joining Bachem.
Briefly, what do you do at Bachem?
I lead the effort in sales of research grade custom synthesis products in the US, Canada and Latin America.
What is your academic background?
I am a Ph. D. biochemist by training.
What do you like to do outside of work?
I love to travel and try different cuisines around the world.
What do you like most about your job?
Every date at work is different. Every project that I work on is unique where we will be able to offer a tailored package to our customers’ need. The chance to continue meeting new customers and learn about new researches makes it always exciting.
Thank you very much Pete.