Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.

Tammar wallaby mammary cathelicidins are differentially expressed during lactation and exhibit antimicrobial and cell proliferative activity

Cathelicidins secreted in milk may be central to autocrine feedback in the mammary gland for optimal development in addition to conferring innate immunity to both the mammary gland and the neonate. This study exploits the unique reproductive strategy of the tammar wallaby (Macropus eugenii) model to analyse differential splicing of cathelicidin genes and to evaluate the bactericidal activity and effect of the protein on mammary epithelial cell proliferation. Two linear peptides, Con73 and Con218, derived from the heterogeneous carboxyl end of cathelicidin transcripts, MaeuCath1 and MaeuCath7 respectively, were evaluated for antimicrobial activity. Both Con73 and Con218 significantly inhibited the growth of Staphylococcus aureus, Pseudomonas aureginosa, Enterococcus faecalis and Salmonella enterica. In addition both MaeuCath1 and MaeuCath7 stimulated proliferation of primary tammar wallaby mammary epithelial cells (WallMEC). Lactation-phase specific alternate spliced transcripts were determined for MaeuCath1 showing utilisation of both antimicrobial and proliferative functions are required by the mammary gland and the suckled young. The study has shown for the first time that temporal regulation of milk cathelicidins may be crucial in antimicrobial protection of the mammary gland and suckled young and mammary cell proliferation.

Peptide mimics targeting bacterial membranes

In recent years, society has been increasingly concerned with bacteria that are no longer susceptible to commercial antibiotics. Faced with a lack of tools, medical practitioners today are forced to prescribe medicines that, although effective, cause as much harm to the patient as the principal infection. The purpose of this research project is to develop novel antibacterials that remain potent against bacterial infections without being toxic to the patient.

Bioactive proteins and peptides from soybeans.

Dietary proteins from soybeans have been shown to offer health benefits in vivo and/or in vitro either as intact proteins or in partially digested forms also called bioactive peptides. Upon oral administration and absorption, soy-derived bioactive peptides may induce several physiological responses such as antioxidative, antimicrobial, antihypertensive, anticancer and immunomodulatory effects. There has therefore been a mounting research interest in the therapeutic potential of soy protein hydrolysates and their subsequent incorporation in functional foods and 'Food for Specified Health Uses' (FOSHU) related products where their biological activities may assist in the promotion of good health or in the control and prevention of diseases. This mini review discusses relevant patents and gives an overview on bioactive proteins and peptides obtainable from soybeans. Processes for the production and formulation of these peptides are given, together with specific examples of their therapeutic potential and possible areas of application.

Food-derived multifunctional bioactive proteins and peptides: sources and production

Multifunctional proteins and peptides from food proteins have been studied over the past few decades to elucidate their biological potency and the beneficial roles they play in human health. Owing to their multiple biological activities, these peptides have a wider role in modulating physiological functions such as antioxidative, antimicrobial, antihypertensive, cytomodulatory, anxiolytic, anorexic, and immunomodulatory activities in living body systems. Highlighted in this chapter is the biological role of some multifunctional peptides as well as the food proteins and enzyme(s) that are responsible for their release. Other challenges to the bioprocessing of multifunctional peptides and the need for research to address them are also discussed.