Peptide Applications

Today, we share a significant study led by Jessica R. Kramer's team, published in Advanced Materials. This research reports a highly potent and cost-effective novel antifreeze polypeptide synthesized from alanine (Ala) and glutamic acid (Glu) via two scalable polymerization methods. At low concentrations (µg mL⁻¹), this polypeptide efficiently inhibits ice recrystallization (IRI), demonstrating activity comparable to natural fish antifreeze proteins. It also possesses excellent properties including good biocompatibility, biodegradability, and thermal reversibility. The study further confirms that this polypeptide effectively protects the activity of model protein therapeutics (e.g., lactate dehydrogenase, antibodies) during repeated freeze-thaw cycles and can inhibit ice crystal coarsening in frozen foods, showcasing broad application prospects in biomedicine and the food industry.

Today, we share important research led by the team of Yiyun Cheng/Jingjing Hu from East China Normal University, published in Bioactive Materials. Addressing key delivery bottlenecks for therapeutic peptides, such as poor cell membrane permeability and difficult tissue penetration, this study developed a novel class of enhanced fluorinated cationic cell-penetrating peptides (eFPPs). Through systematic library construction and screening, the research team successfully identified fluorinated hexa-arginine (FR6) as the optimal "super-enhancer". FR6 not only efficiently promotes the intracellular delivery and endosomal escape of various peptides via a unique synergistic effect between its fluoroalkyl chains and arginine residues, but also demonstrates exceptional transdermal delivery capabilities. In animal models, FR6 significantly enhanced the anti-tumor efficacy of the pro-apoptotic peptide KLA and successfully enabled effective treatment of UVB-induced skin photoaging with the anti-aging peptide AHP-8. This work provides a novel, versatile delivery platform to overcome the biological barriers of peptide drugs.

Today, we share a significant study published in Nature Nanotechnologyby a collaborative team led by Jiacan Su from Shanghai Jiao Tong University and Xiaoyuan Chen from the National University of Singapore, among others. This research tackles the major challenge of inefficient drug delivery to diseased chondrocytes in osteoarthritis (OA) therapy. Inspired by viral infection mechanisms, the team designed a nanomicelle functionalized with a virus glycoprotein-mimetic peptide. This intelligent delivery system achieves simultaneous cartilage tissue retention and specific uptake by diseased cells, demonstrating remarkable cartilage protection in both small and large animal models. It offers an efficient nanodelivery platform for developing disease-modifying osteoarthritis drugs (DMOADs).

Today, we share research published in Cell Research, reporting a novel immune evasion mechanism in colorectal cancer (CRC) that is independent of the canonical Wnt/β-catenin signaling. The study found that loss-of-function mutations in the APCgene, present in 80-90% of CRC cases, lead to the activation of the protein tyrosine phosphatase PTPN13. This, in turn, dephosphorylates and inhibits the key immune transcription factor STAT1. Consequently, downstream IRF1 expression is downregulated, the MHC class I antigen presentation pathway is impaired, ultimately weakening CD8+ T cell infiltration and function, and promoting tumor immune evasion. Based on this mechanism, the research team developed a peptide derived from the 11 C-terminal amino acids of the APC protein (APC11). This peptide effectively blocks the interaction between PTPN13 and STAT1, restoring anti-tumor immune responses. In various preclinical models, the APC11 peptide, used either alone or in combination with anti-PD-1 antibodies, demonstrated significant tumor-suppressive effects, providing a new target and strategy for immunotherapy in APC-mutant CRC.

Today, we share groundbreaking research by the team of Samuel I. Stupp, published in Advanced Materials. This study successfully developed a water-soluble, self-assembling novel organic ferroelectric material by inducing symmetry breaking through peptide molecules. This material not only exhibits an ultralow driving voltage (±2.5 kV/cm) but also significantly promotes the growth of neuronal axons. This work opens a new avenue for developing water-processable, biocompatible ferroelectric biomaterials, bringing new possibilities for bioelectronic devices and neural regenerative medicine.

Globally, with the increasing number of immunocompromised patients, advancements in intensive care, and the widespread use of immunosuppressive drugs, the incidence and mortality rates of invasive fungal infections are continuously rising. Facing this severe challenge, the World Health Organization (WHO), for the first time in 2022, released a "Fungal Priority Pathogens List," categorizing Candida auris, Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicansas "critical priority" pathogens. These fungi not only possess multidrug resistance but also exhibit strong capabilities in biofilm formation and host immune evasion mechanisms, leading to frequent failures of existing antifungal drugs in clinical treatment.

In this context, Antimicrobial Peptides (AMPs), as an emerging therapeutic strategy, are garnering high attention from scientists and clinicians. The review titled "Repositioning Antimicrobial Peptides Against WHO‐Priority Fungi" published in Advanced Sciencesystematically revisits the mechanisms, optimization strategies, and application prospects of AMPs in antifungal therapy, offering new ideas to combat drug-resistant fungi.

Today, we are sharing a significant research article published in the journal Cell. This study employed a machine learning-based approach to predict nearly one million novel Antimicrobial Peptides (AMPs) from the global microbiome, encompassing 63,410 metagenomes and 87,920 high-quality prokaryotic genomes. The research established a comprehensive, open-access resource named AMPSphere, containing 863,498 non-redundant candidate AMPs (c_AMPs). The team synthesized 100 predicted peptides for experimental validation, finding that 79 exhibited antibacterial activity in vitro, and 63 effectively targeted ESKAPEE pathogens. Further investigations using structural biology, biochemistry, and murine infection models confirmed that these peptides function by disrupting bacterial membranes. Notably, some lead compounds demonstrated in vivoanti-infective efficacy comparable to clinical antibiotics. This work not only reveals the vast diversity of AMPs within the microbiome, providing a novel molecular library to combat antibiotic resistance, but also powerfully demonstrates the enormous potential of artificial intelligence in accelerating antimicrobial drug discovery.