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Research advances in the antimicrobial activity of natural product-antimicrobial peptide (AMP) mimic conjugates

Ayue Kang1, Yue Tian1, Yan Wang1

  • 1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China.

Bioorganic Chemistry
|February 11, 2026
PubMed

Insights

Novel antimicrobial peptides (AMPs) derived from natural products show promise against drug-resistant bacteria like MRSA. Combining natural products with AMP mimics offers a viable strategy to overcome limitations like cytotoxicity and develop new antibiotics.

Area of Science:

  • Drug discovery and development
  • Infectious diseases
  • Microbiology

Background:

  • Antimicrobial resistance (AMR) is a global health crisis, leading to increased mortality.
  • Existing antibiotic pipelines are insufficient to combat evolving drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA).
  • Antimicrobial peptides (AMPs) show potential but face challenges in clinical translation due to cytotoxicity and hemolytic activity.

Purpose of the Study:

  • To review recent advancements in conjugates combining natural products with AMP mimics.
  • To discuss the antibacterial activity, structure-activity relationships (SARs), and mechanisms of action of these conjugates.
  • To provide insights for developing novel antimicrobials using natural products and AMPs.

Main Methods:

  • Literature review of natural product-AMP mimic conjugates.
  • Analysis of antibacterial activity and SARs.
  • Elucidation of mechanisms of action for representative conjugates.

Main Results:

  • Natural products combined with AMP mimics demonstrate promising antibacterial activity against resistant strains.
  • SAR studies reveal key features influencing efficacy and safety.
  • Mechanisms of action involve membrane targeting and other pathways, with low potential for resistance induction.

Conclusions:

  • Conjugates of natural products and AMP mimics offer a promising strategy to address the AMR crisis.
  • This approach can overcome the limitations of traditional AMPs, such as poor druggability.
  • Rational design based on these conjugates can lead to the development of next-generation antimicrobials.
Keywords:
Antibacterial mechanismAntimicrobial peptides (AMPs)ConjugateNatural productStructure-activity relationships (SARs)

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