Oligomerisation of tryptocidine C, a Trp-rich cyclodecapeptide from the antimicrobial tyrothricin complex

Rautenbach, Marina; Kumar, Vikas; Vosloo, J. Arnold; Masoudi, Yasamin; Wyk, R. J.; Stander, Maria A.

doi:10.1016/j.biochi.2020.12.006

Cited by 6 publications

(26 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The change in the first 60 min was investigated by measuring the total Trp fluorescence over the Trc mix dose-response concentration range (100 to 1.25 µg/mL) with E4M and A4M as representative cellulose formulants. Our results corroborated previous observations [ 34 , 36 , 39 , 40 , 46 ] that the Trc mix environment has a major influence on oligomerisation behaviour ( Figure 4 ).…”

Section: Resultssupporting

confidence: 93%

“…The presence of four aromatic amino acid residues and three hydrophobic residues in tyrocidines (refer to Figure 1 C) could drive hydrophobic interactions in aqueous systems between the peptides to form oligomers. This oligomerisation leads to the change in their optical character, such as far-UV circular dichroism [ 40 , 46 ] and fluorescence emission [ 40 , 43 ], as well as possibly changing their biological activity.…”

Section: Resultsmentioning

confidence: 99%

“…A recent study showed that tryptocidine C, a Trp-rich analogue found in the Trc mix, formed defined nanoparticles and that the oligomerisation can be followed by electrospray mass spectrometry and fluorescence [ 40 ]. In this study, we observed the oligomerisation of the peptides to form dimers, trimers and tetramers via electrospray mass spectrometry, as depicted in Figure 2 .…”

Section: Resultsmentioning

confidence: 99%

“…However, the fact that the cellulose derivatives stabilised Trp fluorescence can be contributed to the interaction of cellulose derivatives with the cyclodecapeptides in the Trc mix. This interaction can prevent or slow down the formation and dynamic rearrangement of oligomers [ 40 , 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

“…Trcs exhibit their amphipathic character only as b-sheet dimers [ 32 , 33 ], which have been proposed to be the active conformation correlated to their membranolytic antimicrobial activity [ 31 ]. Furthermore, the range of activity of the Trcs is highly dependent on their oligomerisation profile [ 36 , 37 , 38 ], as the Trcs readily form aggregates or higher-order oligomers [ 33 , 34 , 36 , 39 ], including highly ordered nanostructures [ 40 ]. This oligomerisation is dynamic and depends on the solvent environment, cyclodecapeptide identity and feedstock concentration [ 33 , 34 , 36 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Influence of Cellulose-Type Formulants on Anti-Candida Activity of the Tyrocidines

Masoudi¹,

Rensburg²,

Barnard-Jenkins³

et al. 2021

Antibiotics

Self Cite

View full text Add to dashboard Cite

Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the need for combinational therapies. Tyrocidines are cyclic antimicrobial peptides that have shown synergistic activity with antifungal drugs such as caspofungin and amphotericin B. However, these cyclodecapeptides have haemolytic activity and cytotoxicity, but they have been used for decades in the clinic for topical applications. The tyrocidines tend to form higher-order structures in aqueous solutions and excessive aggregation can result in variable or diminished activity. Previous studies have shown that the tyrocidines prefer ordered association to celluloses. Therefore, a formulation with soluble cellulose was used to control the oligomer stability and size, thereby increasing the activity against Candida spp. Of the formulants tested, it was found that commercial hydroxy-propyl-methyl cellulose, E10M, yielded the best results with increased stability, increased anti-Candida activity, and improved selectivity. This formulation holds promise in topical applications against Candida spp. infections.

show abstract