ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
AI-Based D-Amino Acid Substitution for Optimizing Antimicrobial Peptides to Treat Multidrug-Resistant Bacterial Infection.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Next-Generation Antimicrobial Peptides for Biofilm-Associated Infections: Engineering, Biomaterial Delivery and AI-Assisted Discovery.Antibiotics (Basel, Switzerland) · 2026Review
- NIR-Triggered On-Demand Synergistic Therapy for Multidrug-Resistant Bacterial Infections Via a Smart Phase-Transition Hydrogel.Advanced healthcare materials · 2026Article
- Antimicrobial Peptides Based on the TisB Toxin: Toward Enhanced Activity and Synergy with Antibiotics.ACS omega · 2026Article
- De Novo Multi-Mechanism Antimicrobial Peptide Design via Multimodal Deep Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rationally Engineered D-Amino Acid Peptide DT7-3 Combats Multidrug-ResistantMicroorganisms · 2026Article
- AI-Based D-Amino Acid Substitution for Optimizing Antimicrobial Peptides to Treat Multidrug-Resistant Bacterial Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
D-amino acid substitution provides an effective strategy for optimizing antimicrobial peptides (AMPs) by enhancing their stability. However, the absence of universal rules renders traditional screening methods time-consuming and labor-intensive, potentially leading to reduced or complete loss of activity. Here, we curated a D-amino acid-substituted AMP dataset from published literature and databases. We then developed ADAPT, an AI-based tool for predicting the functional impact of D-amino acid substitutions, and integrated it into a high-throughput screening pipeline for AMP optimization. Of the variants obtained through this pipeline, 80% exhibited enhanced antibacterial activity. Among these, dR2-1 showed exceptional broad-spectrum antimicrobial activity, reduced toxicity, and substantially improved stability. Mechanistic studies confirmed a membrane-targeting antibacterial mode of action. Furthermore, we engineered a hydrogel delivery system that effectively treated cutaneous infections in mice. Overall, our study established an AI-based framework for D-amino acid substitution in AMPs, enabling the efficient discovery of potent and stable candidates with enhanced clinical translation potential.
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Registered trials
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