Polymers with tunable side-chain amphiphilicity as non-hemolytic antibacterial agents

Uppu, Divakara S. S. M.; Akkapeddi, Padma; Manjunath, Goutham B.; Yarlagadda, Venkateswarlu; Hoque, Jiaul; Haldar, Jayanta

doi:10.1039/c3cc43751e

Cited by 107 publications

(128 citation statements)

References 17 publications

(4 reference statements)

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…These polymers were found to be stable in buffer (at pH = 7.4). The chemically synthesized degradation byproducts of Qn-prP were found to lose the antibacterial activity (MIC > 1000 µg mL -1 ) and were also non-hemolytic (HC 50 > 10000 µg mL -1 ) [54].…”

Section: Antibacterial Activity and Mammalian Cellmentioning

confidence: 99%

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

et al. 2016

Self Cite

View full text Add to dashboard Cite

Section: Antibacterial Activity and Mammalian Cellmentioning

confidence: 99%

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

et al. 2016

Self Cite

View full text Add to dashboard Cite

“…[22] Several excellent designs have been effectively used to obtain ap lethora of antimicrobial polymers.…”

Section: Macromolecular Approachmentioning

confidence: 99%

Membrane‐Active Small Molecules: Designs Inspired by Antimicrobial Peptides

2015

Self Cite

View full text Add to dashboard Cite

Infectious diseases continue to be one of the major contributors to human morbidity. The rapid rate at which pathogenic microorganisms have developed resistance against frontline antimicrobials has compelled scientists to look for new alternatives. Given their vast antimicrobial repertoire, substantial research effort has been dedicated toward the development of antimicrobial peptides (AMPs) as alternative drugs. However, inherent limitations of AMPs have driven substantial efforts worldwide to develop synthetic mimics of AMPs. This review focuses on the progress that has been made toward the development of small molecules that emulate the properties of AMPs, both in terms of design and biological activity. Herein we provide an extensive discussion of the structural features of various designs and we examine biological properties that have been exploited. Furthermore, we raise a number of questions for which the field has yet to provide solutions and discuss possible future research directions that remain either unexploited or underexploited.

show abstract

“…The samples were then transferred to cuvettes, and fluorescence was measured using an F-2500 fluorescence spectrophotometer (Hitachi, Japan) at 350 nm (excitation wavelength) and 420 nm (emission wavelength). The inner membrane permeabilization activity of the peptides was measured by the uptake of propidium iodide (PI) (14,15). The collected cells were washed and resuspended as described above, and then 10 M PI was added to the cells and the reaction mixture was incubated for 30 min at 25°C.…”

Section: Organisms the Multidrug-resistant (Mdr) Clinical Isolates Mmentioning

confidence: 99%

“…The cytoplasmic membrane depolarization activities of the peptides were determined using the membrane potential-sensitive dye disC 3 (5) (3,3=-dipropylthiadicarbocyanine iodide) (14). The harvested E. coli ATCC 35218 cells collected at different time points were washed with 5 mM HEPES and 5 mM glucose and were resuspended in 5 mM glucose-5 mM HEPES buffer-100 mM KCl solution in a 1:1:1 ratio.…”

Section: Organisms the Multidrug-resistant (Mdr) Clinical Isolates Mmentioning

confidence: 99%

The Disulfide Bond of the Peptide Thanatin Is Dispensible for Its Antimicrobial Activity In Vivo and In Vitro

Niu

Zhou

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

b Thanatin (THA) displays potent antibiotic activity, especially against extended-spectrum-␤-lactamase (ESBL)-producing Escherichia coli both in vitro and in vivo, with minimal hemolytic toxicity and satisfactory stability in plasma. However, the high cost of thanatin significantly limits its development and clinical application. To reduce the cost of peptide synthesis, a formulation of cyclic thanatin (C-thanatin) called linear thanatin (L-thanatin) was synthesized and its activity was evaluated in vivo and in vitro. Results showed that C-thanatin and L-thanatin MICs did not differ against eight Gram-negative and two Gram-positive bacterial strains. Furthermore, the survival rates of ESBL-producing-E. coli-infected mice were consistent after C-thanatin or L-thanatin treatment at 5 or 10 mg/kg of body weight. Neither C-thanatin nor L-thanatin showed toxicity for human red blood cells (hRBCs) and human umbilical vein endothelial cells (HUVECs) at a concentration as high as 256 g/ml. Results of circular dichroism spectroscopy indicated that the secondary structure of L-thanatin is extremely similar to that of C-thanatin. Membrane permeabilization and depolarization assays showed that C-thanatin and L-thanatin have similar abilities to permeabilize the outer and inner membranes and to induce membrane depolarization in ESBL-producing E. coli. However, neither of them caused significant HUVEC membrane permeability. These findings indicate that the two peptides have similar effects on bacterial cell membranes and that the disulfide bond in thanatin is not essential for its antimicrobial activities in vivo and in vitro. L-thanatin is thus a promising low-cost peptide candidate for treating ESBL-producing E. coli infections. T hanatin (THA) is a cationic antimicrobial peptide that was first discovered in the hemipteran insect Podisus maculiventris.This peptide is composed of 21 amino acids (GSKKPVPIIYCNR RTGKCQRM), with an intramolecular disulfide bridge between the two cysteines at positions 11 and 18. Our previous studies revealed that thanatin exhibits potent antibiotic activity, especially against extended-spectrum-␤-lactamase (ESBL)-producing Esc herichia coli, both in vitro and in vivo, with a low inherent ability to induce microbial resistance, minimal hemolytic toxicity, and high stability in plasma (1, 2).Despite their promise for clinical benefit, the high cost of producing peptide drugs such as thanatin significantly limits their development and clinical application. Compared with conventional antibiotics, the costs of cationic antimicrobial peptides are always prohibitively high for large-scale production (3). Intrachain disulfide bonds exist in many naturally occurring peptides and play important roles in biological activities. However, synthesis of peptide drugs with one or more disulfide bridges is complicated and expensive (4).Previous studies found that the disulfide bonds of protegrin-1 are not essential for its antimicrobial and hemolytic activities in vitro (5). To reduce the cost of thanatin synthes...

show abstract

Polymers with tunable side-chain amphiphilicity as non-hemolytic antibacterial agents

Cited by 107 publications

References 17 publications

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

Membrane‐Active Small Molecules: Designs Inspired by Antimicrobial Peptides

The Disulfide Bond of the Peptide Thanatin Is Dispensible for Its Antimicrobial Activity In Vivo and In Vitro

Contact Info

Product

Resources

About