Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0268596 (
EMA
)
2,520
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Amphiphilic methacrylate co-polymers recently demonstrated antimicrobial activity. To understand their activity mechanism, we prepared three homologous methacrylate co-polymers with activity ranging from inactive (MMA) over specifically active (
EMA
) to non-specifically active (BMA) against bacteria and human erythrocytes. Fluorescent dye leakage assays were used to characterize their membrane-disrupting activity against liposomes of different compositions. From bacterial membrane-mimicking liposomes (composed of Escherichia coli extract or 20:80 DOPG/
DOPE
), the two active forms,
EMA
and BMA, caused more dye leakage than the inactive MMA, which mirrors their antibacterial activity trend. From mammalian membrane-mimicking liposomes (composed of DOPC or 20:80 DOPG/DOPC), the highly hemolytic BMA caused significantly more leakage than MMA and
EMA
, which mirrors its hemolytic activity trend. Moreover, to dissect the effect of intrinsic membrane curvature from that of membrane charge, we used a ternary membrane with constant charge and tunable intrinsic curvature. Specifically, we used membranes composed of DOPG/
DOPE
/DOPC with constant DOPG content and varying
DOPE
/DOPC ratio. To significantly disrupt this model, methacrylate co-polymers with different activity profiles required a different minimum threshold
DOPE
content. In contrast, variation in DOPG/DOPC ratio at constant
DOPE
concentration did not show a similar influence on the selective membrane-disrupting activity of these co-polymers. Our results suggested that the intrinsic membrane curvature, rather than membrane charge, may play a major role in the selective membrane-disrupting activity of methacrylate co-polymers. Since more PE lipids exist in bacterial membranes than in eukaryotic membranes, our results imply that negative-intrinsic-curvature lipids such as PE may contribute to the selective antimicrobial activity.
...
PMID:Lipid composition influences the membrane-disrupting activity of antimicrobial methacrylate co-polymers. 2102 18