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Record W2801208649 · doi:10.3390/biom8020019

Improving the Activity of Trp-Rich Antimicrobial Peptides by Arg/Lys Substitutions and Changing the Length of Cationic Residues

2018· article· en· W2801208649 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueBiomolecules · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAntimicrobial Peptides and Activities
Canadian institutionsUniversity of Calgary
FundersAlberta Innovates
KeywordsCationic polymerizationChemistryAntimicrobial peptidesAntimicrobialPeptideBiochemistryCombinatorial chemistryStereochemistryOrganic chemistry

Abstract

fetched live from OpenAlex

Antimicrobial peptides (AMPs) constitute a promising alternative for the development of new antibiotics that could potentially counteract the growing number of antibiotic-resistant bacteria. However, the AMP structure–function relationships remain unclear and detailed studies are still necessary. The positively charged amino acid residues (Arg and Lys) play a crucial role in the activity of most AMPs due to the promotion of electrostatic interactions between the peptides and bacterial membranes. In this work we have analyzed the antimicrobial and structural properties of several Trp-rich AMPs containing exclusively either Arg or Lys as the positively charged residues. Their antimicrobial activity and mechanism of action were investigated, showing that Lys residues give rise to a reduced antimicrobial potency for most peptides, which was correlated, in turn, with a decrease in their ability to permeabilize the cytoplasmic membrane of Escherichia coli. Additionally, the presence of Arg and Lys renders the peptides susceptible to degradation by proteases, such as trypsin, limiting their therapeutic use. Therefore, modifications of the side chain length of Arg and Lys were investigated in an attempt to improve the protease resistance of AMPs. This approach resulted in enhanced stability to trypsin digestion, and in several cases, shorter sidechains conserved or even improved the antimicrobial activity. All together, these results suggest that Arg-to-Lys substitutions, coupled with side chain length modifications, can be extremely useful for improving the activity and stability of AMPs.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.857

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.002
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.225
Teacher spread0.215 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it