ArticleFrontiers in microbiology2020
D- and Unnatural Amino Acid Substituted Antimicrobial Peptides With Improved Proteolytic Resistance and Their Proteolytic Degradation Characteristics.
Article in Frontiers in microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 232 citations in OpenAlex.
- In Vitro Screening of Short Synthetic Antimicrobial Peptides Toward Food-Relevant Microorganisms: Antifungal Activity and Molecular Docking Analysis.Microorganisms · 2026Article
- Next-Generation Antimicrobial Peptides for Biofilm-Associated Infections: Engineering, Biomaterial Delivery and AI-Assisted Discovery.Antibiotics (Basel, Switzerland) · 2026Review
- Multivalent Display of Antimicrobial Peptides on Plant Virus Scaffolds Enhances Killing of Drug-Resistant Bacteria.ACS nano · 2026Article
- Marine Antimicrobial Peptides: From Ocean Biodiversity to Genome Mining, Multi-Omics Discovery, and Biotechnological Innovation in the Battle Against Antimicrobial Resistance.Probiotics and antimicrobial proteins · 2026Review
- Article
- Emerging Technologies for Oral Peptide Delivery: From Bioinspired Systems to Smart Device-Assisted Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Discovery of a Novel Tripeptide Linker that Broadens the Therapeutic Window of Auristatin-Based Antibody-Drug Conjugates by Reducing Bone Marrow Toxicity.Bioconjugate chemistry · 2026Article
- Tyrosine-capped gold nanoparticles enable cysteine-free peptide loading, enhancing the antipseudomonal efficacy of scorpion-derived AamAP1-Lys-NHJournal of materials chemistry. B · 2026Article
- A Comprehensive Review of Antimicrobial Peptides and Smart Biomaterials in Chronic Wound Therapy: Overcoming Biofilms, Resistance, and Translational Barriers.International journal of molecular sciences · 2026Review
- Elucidation of the Antimycobacterial Activity of D-Form Human Lactoferricin 1-11 (D-Form hLF 1-11) AgainstAntibiotics (Basel, Switzerland) · 2026Article
- Optimized LL-37-Derived Peptides Exhibit Antitubercular Activity, Induce Membrane Disruption, and P-Type ATPase Transcriptional Responses inBiomolecules · 2026Article
- Rationally Engineered D-Amino Acid Peptide DT7-3 Combats Multidrug-ResistantMicroorganisms · 2026Article
- Artificial Intelligence-Driven Discovery and Optimization of Antimicrobial Peptides Targeting ESKAPE Pathogens and Multidrug-Resistant Fungi.Microorganisms · 2026Review
- Peptide-based ligand antagonists block a Vibrio cholerae adhesin.FEBS letters · 2026Article
- The rise and future of peptide-based antimicrobials.Journal of microbiology (Seoul, Korea) · 2026Review
- Design, synthesis, molecular docking, and antimicrobial evaluation of hybrid peptides incorporating unnatural amino acids with enhanced hydrophobic sidechains.RSC advances · 2026Article
- The Potential of Non-Ribosomal Peptide Engineering for Creating New Antimicrobial Complexes.Molecules (Basel, Switzerland) · 2026Review
- D-amino acid substitution and cyclization enhance the stability and antimicrobial activity of arginine-rich peptides.Microbiology (Reading, England) · 2026Article
- Natural and Synthetic Peptides as Alternatives to Antibiotics in Intestinal Infections-A Review.Antibiotics (Basel, Switzerland) · 2026Review
- A Comprehensive Review on Non-natural Amino Acid-based Modifications in Antibacterial Peptides.Mini reviews in medicinal chemistry · 2026Review
72 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transition of antimicrobial peptides (AMPs) from the laboratory to market has been severely hindered by their instability toward proteases in biological systems. In the present study, we synthesized derivatives of the cationic AMP Pep05 (KRLFKKLLKYLRKF) by substituting L-amino acid residues with D- and unnatural amino acids, such as D-lysine, D-arginine, L-2,4-diaminobutanoic acid (Dab), L-2,3-diaminopropionic acid (Dap), L-homoarginine, 4-aminobutanoic acid (Aib), and L-thienylalanine, and evaluated their antimicrobial activities, toxicities, and stabilities toward trypsin, plasma proteases, and secreted bacterial proteases. In addition to measuring changes in the concentration of the intact peptides, LC-MS was used to identify the degradation products of the modified AMPs in the presence of trypsin and plasma proteases to determine degradation pathways and examine whether the amino acid substitutions afforded improved proteolytic resistance. The results revealed that both D- and unnatural amino acids enhanced the stabilities of the peptides toward proteases. The derivative DP06, in which all of the L-lysine and L-arginine residues were replaced by D-amino acids, displayed remarkable stability and mild toxicity
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