Ultrashort cationic lipopeptides and lipopeptoids: Evaluation and mechanistic insights against epithelial cancer cells

Domalaon, Ronald; Findlay, Brandon; Ogunsina, Makanjuola; Arthur, Gilbert; Schweizer, Frank

doi:10.1016/j.peptides.2016.07.007

Cited by 30 publications

(48 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fluorescence measurement was conducted to monitor the extent of fibril formation of hIAPP [11][12][13][14][15][16][17][18][19][20] by LS55 Fluorescence Spectrofluorometer system (PerkinElmer Inc, UK). Time curves of thermophoresis for binding affinity were obtained on the microscale thermophoresis (MST) setup (Monolith NT.115 system, NanoTemper Technologies GmbH, Germany).…”

Section: Apparatusmentioning

confidence: 99%

“…The detailed principle and theory have been reported before. [31] In the present study, it relies on the detection of the difference of fluorescence signal intensity caused by the directional movement of FITC label on the hIAPP [11][12][13][14][15][16][17][18][19][20] (FITClabeled hIAPP [11][12][13][14][15][16][17][18][19][20] ) along the temperature gradient in microenvironment. The affinities of molecular interactions were measured by titration experiments in the equilibrium state.…”

Section: Background Of Thermophoresismentioning

confidence: 99%

“…As lipopeptides have some hydrophobic groups, which are similar to the reported aggregation inhibitors, and some lipopeptides could prevent cells from depositing of amyloid fibrils, several potential lipopeptide inhibitors have been engineered and synthesized, which have been assessed for their inhibitory effect in preventing amyloid fibrils formation of hIAPP [11][12][13][14][15][16][17][18][19][20] by using the conventional thioflavin-T fluorescence assay and new technique microscale thermophoresis (MST). The final amyloid fibrils of hIAPP [11][12][13][14][15][16][17][18][19][20] were characterized by transmission electron microscopy. Results suggested that with the increasing length of alkyl chain, the antiaggregation efficiency of lipopeptide inhibitors towards hIAPP 11-20 increased gradually.…”

mentioning

confidence: 99%

“…On the basis of our previous study about different synthesized peptides modulating the self-assembly [30] of hIAPP [11][12][13][14][15][16][17][18][19][20] , most of the inhibitors that could effectively inhibit amyloid formation possess hydrophobic amino acids. Hence, in this study, several potential lipopeptide inhibitors containing hydrophobic alkyl chains and hydrophilic amino acids as head group have been engineered and synthesized, Cx-RRRR-NH 2 (x = 4, 6, 8, 10, 12, and 14; lipopeptides with x carbon atoms) and C14-Rn-NH 2 (n = 2, 3, 4, and 5; lipopeptides with n arginines) ( Figure 1).…”

mentioning

confidence: 99%

“…Hence, in this study, several potential lipopeptide inhibitors containing hydrophobic alkyl chains and hydrophilic amino acids as head group have been engineered and synthesized, Cx-RRRR-NH 2 (x = 4, 6, 8, 10, 12, and 14; lipopeptides with x carbon atoms) and C14-Rn-NH 2 (n = 2, 3, 4, and 5; lipopeptides with n arginines) ( Figure 1). The extent of hIAPP [11][12][13][14][15][16][17][18][19][20] fibrilization under the influence of these inhibitors was assessed, and the binding events between amyloidogenic peptides and inhibitors were investigated. This study will help to deduce a rational template of lipopeptide inhibitor design for hIAPP.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Mao

et al. 2017

Journal of Peptide Science

View full text Add to dashboard Cite

Type 2 diabetes mellitus, a kind of conformational disease, has become an epidemic disease, which seriously endangers the quality of life and health of human beings. The deposition of human islet amyloid polypeptide (hIAPP) has been considered as one of the major pathological features of type 2 diabetes mellitus. As lipopeptides have some hydrophobic groups, which are similar to the reported aggregation inhibitors, and some lipopeptides could prevent cells from depositing of amyloid fibrils, several potential lipopeptide inhibitors have been engineered and synthesized, which have been assessed for their inhibitory effect in preventing amyloid fibrils formation of hIAPP [11][12][13][14][15][16][17][18][19][20] by using the conventional thioflavin-T fluorescence assay and new technique microscale thermophoresis (MST). The final amyloid fibrils of hIAPP [11][12][13][14][15][16][17][18][19][20] were characterized by transmission electron microscopy. Results suggested that with the increasing length of alkyl chain, the antiaggregation efficiency of lipopeptide inhibitors towards hIAPP 11-20 increased gradually.Meanwhile, the amount of arginines, which represent the head groups of lipopeptides, may also have some influence. The binding events also showed that the inhibitory efficiency of these lipopeptide inhibitors was enhanced with the increase of affinities between lipopeptides and hIAPP [11][12][13][14][15][16][17][18][19][20] , which were obtained from MST. This study demonstrated the efficiency of lipopeptides in inhibiting the aggregation of hIAPP [11][12][13][14][15][16][17][18][19][20] and proved that MST could be regarded as an appropriate and rapid method to screen potential inhibitors of hIAPP [11][12][13][14][15][16][17][18][19][20] or other amyloid proteins. This study also broadens the types of inhibitors on inhibiting amyloid formation of hIAPP.

show abstract

Section: Apparatusmentioning

confidence: 99%

Section: Background Of Thermophoresismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Mao

et al. 2017

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

Amphiphilic lysine conjugated to tobramycin synergizes legacy antibiotics against wild‐type and multidrug‐resistant Pseudomonas aeruginosa

et al. 2018

Self Cite

View full text Add to dashboard Cite

Peptidomimetic modification is a common route of optimization for biologically active peptides. Previous studies in our group have shown that conjugation of amphiphilic tobramycin to other antibacterials enhance their latent outer membrane permeabilizing and efflux blocking activity toward Gram-negative pathogens including Pseudomonas aeruginosa. Herein, we describe the antimicrobial adjuvant properties of amphiphilic lysine ligated to tobramycin. The most potent amphiphilic lysine-tobramycin conjugate 3 potentiated the antibacterial efficacy of 8 clinically used antibiotics against wild type, multidrug- and extensively drug-resistant P. aeruginosa isolates from Canadian hospitals whereas amphiphilic lysine 4 did not. Antibiotics that are synergistic with conjugate 3 included moxifloxacin, ciprofloxacin, erythromycin, chloramphenicol, trimethoprim, novobiocin, linezolid, and fosfomycin. Out of these 8 antibiotics, novobiocin showed highest synergy.

show abstract

Evaluation of l‐2,4‐diaminobutyric acid‐based ultrashort cationic lipopeptides as potential antimicrobial and anticancer agents

Boda

Caluag

Dante

et al. 2021

J Chinese Chemical Soc

View full text Add to dashboard Cite

Ultrashort cationic lipopeptides (USCLs) are amphiphiles that exhibit antimicrobial and anticancer activity. They are composed of an aliphatic chain attached to a positively charged peptide group consisting of a few amino acid residues. Here, we report the activity of a series of l‐2,4‐diaminobutyric acid (Dab)‐rich USCLs with varying N‐acyl chain length and charge against Escherichia coli, Staphylococcus aureus, Candida albicans, colon, breast, and lung epithelial cancer cell lines. USCLs with chain lengths of 14–18 carbons showed significant antimicrobial activity with C16‐conjugated peptides being the most active against E. coli and S. aureus, and C18‐conjugated peptides being the most active against C. albicans. Doubly charged USCLs with aliphatic tails that are 14 carbon atoms and longer showed more potent anticancer activity compared to their triply charged counterparts. C14‐Dab2‐NH2 displayed little toxicity to normal cells, and selectivity to microbial and cancer cells over normal cells. Its structural simplicity, bioactivity, nontoxicity, and selectivity make it a promising therapeutic agent.

show abstract

Ultrashort cationic lipopeptides and lipopeptoids: Evaluation and mechanistic insights against epithelial cancer cells

Cited by 30 publications

References 39 publications

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Amphiphilic lysine conjugated to tobramycin synergizes legacy antibiotics against wild‐type and multidrug‐resistant Pseudomonas aeruginosa

Evaluation of l‐2,4‐diaminobutyric acid‐based ultrashort cationic lipopeptides as potential antimicrobial and anticancer agents

Contact Info

Product

Resources

About