Discovery of Antimicrobial Peptide Macrocycles Through Bacterial Display

Randall, Justin R.; DuPai, Cory D.; Davies, Bryan William

doi:10.1007/978-1-0716-1689-5_15

Cited by 9 publications

(11 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the predicted amino acid pattern seen in SBH-15 was recently observed in a large proteomic analysis of the b-hairpin motif (DuPai et al, 2021). Such motif predictions paired with the inclusion of potential cysteine pairs could be used in the design and screening of macrocyclic b-hairpin peptide libraries using SLAY in the future (Randall et al, 2022).…”

Section: Discussionmentioning

confidence: 76%

Synthetic antibacterial discovery of symbah-1, a macrocyclic β-hairpin peptide antibiotic

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 76%

Synthetic antibacterial discovery of symbah-1, a macrocyclic β-hairpin peptide antibiotic

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our randomly selected SynCH peptides were not inherently antibacterial (table S1), so we decided to use a high-throughput genetic platform developed in our laboratory called surface-localized antimicrobial display (SLAY) ( 25 , 26 ) to screen for antibacterial activity. SLAY functions through the inducible display of a plasmid-encoded peptide library on the gram-negative bacterial cell surface.…”

Section: Resultsmentioning

confidence: 99%

“…Detailed methods for library creation have been previously reported ( 25 , 26 ). Briefly, the two library inserts were generated by polymerase chain reaction (PCR) using forward primer oJR557 with reverse primers oJR560 and oJR561 encoding each library.…”

Section: Methodsmentioning

confidence: 99%

“…In cases where triplicate samples differed, the concentration supported by the median of three replicates was reported and shown. SLAY procedure SLAY procedures have been detailed previously (25,26). Briefly, 100 μl of E. coli W3110 frozen cells containing the pooled SynCH plasmid library were recovered in 10 ml of LB supplemented with carbenicillin (75 μg/ml) for 2 hours.…”

Section: Minimum Bactericidal Concentrationmentioning

confidence: 99%

See 1 more Smart Citation

Designing and identifying β-hairpin peptide macrocycles with antibiotic potential

et al. 2023

Self Cite

View full text Add to dashboard Cite

Peptide macrocycles are a rapidly emerging class of therapeutic, yet the design of their structure and activity remains challenging. This is especially true for those with β-hairpin structure due to weak folding properties and a propensity for aggregation. Here, we use proteomic analysis and common antimicrobial features to design a large peptide library with macrocyclic β-hairpin structure. Using an activity-driven high-throughput screen, we identify dozens of peptides killing bacteria through selective membrane disruption and analyze their biochemical features via machine learning. Active peptides contain a unique constrained structure and are highly enriched for cationic charge with arginine in their turn region. Our results provide a synthetic strategy for structured macrocyclic peptide design and discovery while also elucidating characteristics important for β-hairpin antimicrobial peptide activity.

show abstract

“…Our randomly selected SynCH peptides were not inherently antibacterial ( Table 1 ), so we decided to use a high-throughput genetic platform developed in our lab called surface localized antimicrobial display (SLAY) ( 26 , 27 ) to screen for antibacterial activity. SLAY functions through the inducible display of a plasmid encoded peptide library on the Gram-negative bacterial cell surface.…”

Section: Resultsmentioning

confidence: 99%

Designing β-hairpin peptide macrocycles for antibiotic potential

Randall

DuPai

Cole

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Peptide macrocycles are a rapidly emerging new class of therapeutic, yet the design of their structure and activity remains challenging. This is especially true for those with β-hairpin structure due to weak folding properties and a propensity for aggregation. Here we use proteomic analysis and common antimicrobial features to design a large peptide library with macrocyclic β-hairpin structure. Using an activity-driven high-throughput screen we identify dozens of peptides killing bacteria through selective membrane disruption and analyze their biochemical features via machine learning. Active peptides contain a unique constrained structure and are highly enriched for cationic charge with arginine in their turn region. Our results provide a synthetic strategy for structured macrocyclic peptide design and discovery, while also elucidating characteristics important for β-hairpin antimicrobial peptide activity.

show abstract

Discovery of Antimicrobial Peptide Macrocycles Through Bacterial Display

Cited by 9 publications

References 11 publications

Synthetic antibacterial discovery of symbah-1, a macrocyclic β-hairpin peptide antibiotic

Synthetic antibacterial discovery of symbah-1, a macrocyclic β-hairpin peptide antibiotic

Designing and identifying β-hairpin peptide macrocycles with antibiotic potential

Designing β-hairpin peptide macrocycles for antibiotic potential

Contact Info

Product

Resources

About