Applications and Research

The field of research peptides has transitioned from simple hormone replacement to a sophisticated area of precision bioengineering. For researchers, peptides represent a unique modality that bridges the gap between small-molecule drugs and large-scale biologics, offering high specificity with manageable metabolic clearance (Al Musaimi et al., 2025).

The Modern Research Process: AI and “De Novo” Design

In contemporary laboratories, the discovery process has moved beyond simple extraction from natural sources.

  • AI-Driven Discovery: Researchers are now utilizing contrastive conditioned diffusion frameworks (like PepCCD) and generative AI to design peptide sequences with specific target affinities (Zhang et al., 2025). These models can predict how a peptide will fold and bind to “undruggable” protein surfaces before a single residue is synthesized.

  • High-Throughput Screening: Technologies such as mRNA display and phage display allow researchers to screen libraries containing trillions of unique peptide sequences simultaneously to identify high-affinity ligands for specific receptors (Garcia Jimenez et al., 2023).

Key Research Developments (2024–2025)

1. Multireceptor Incretin Agonists

The most visible breakthrough in peptide research involves metabolic regulation. Beyond single-receptor agonists, current research is focused on dual and triple agonists.

  • Mechanisms: These “next-generation” agents target multiple receptors—such as GLP-1, GIP, and Glucagon—simultaneously to achieve synergistic effects on glucose metabolism and weight reduction (Al Musaimi et al., 2025).

  • Pleiotropic Effects: Recent studies (2025) are investigating these peptides for applications beyond weight loss, including neuroprotection in Alzheimer’s and reducing inflammation in chronic kidney disease (CKD) (Perkovic et al., 2024; Al Musaimi et al., 2025).

2. Peptide-Drug Conjugates (PDCs)

PDCs are the “guided missiles” of oncology research. They consist of a homing peptide (targeting a tumor antigen), a cleavable linker, and a cytotoxic payload.

  • Advantage over ADCs: Unlike Antibody-Drug Conjugates (ADCs), PDCs have a lower molecular weight (2–20 kDa), allowing for superior tumor penetration and faster renal clearance, which minimizes systemic toxicity (Al Musaimi et al., 2025).

  • Current Focus: Research is centered on developing more stable linkers that only release the “payload” when triggered by specific enzymes within the tumor microenvironment (Al Musaimi et al., 2025).

3. Macrocycles and Constrained Peptides

To overcome the inherent instability of linear peptides, researchers are focusing on macrocyclization.

  • Stapled Peptides: By introducing chemical “staples” (hydrocarbon bridges) into the peptide backbone, scientists can lock a peptide into an alpha-helical shape. This prevents proteases from “grabbing” and breaking the chain, significantly increasing the peptide’s half-life (Garcia Jimenez et al., 2023).

  • Mirror-Image Screening: Scientists are increasingly exploring D-peptides (non-natural chirality). These “mirror-image” molecules are virtually invisible to the body’s digestive enzymes, offering a potential path to oral peptide delivery (Garcia Jimenez et al., 2023).

Regenerative and Antimicrobial Research

  • Tissue Repair: Peptides like BPC-157 and tripeptides (e.g., KdPT) are being scrutinized for their ability to modulate angiogenesis (vessel growth) and stimulate fibroblast migration in chronic wound healing (GlobalRPH, 2025; Al Musaimi et al., 2025).

  • Antimicrobial Peptides (AMPs): In response to antibiotic resistance, research into AMPs (like mesco-2) focuses on peptides that physically disrupt bacterial membranes rather than interfering with metabolic pathways, making it harder for bacteria to develop resistance (Galzitskaya, 2025).

References

  • Al Musaimi, O., AlShaer, D., de la Torre, B. G., & Albericio, F. (2025). 2024 FDA TIDES (Peptides and Oligonucleotides) Harvest. Pharmaceuticals, 18(3), 291. https://doi.org/10.3390/ph18030291

  • Galzitskaya, O. V. (2025). Creation of New Antimicrobial Peptides 3: Research Promises and Shortcomings. International Journal of Molecular Sciences, 26(24), 11992. https://doi.org/10.3390/ijms262411992

  • Garcia Jimenez, D., Poongavanam, V., & Kihlberg, J. (2023). Macrocycles in Drug Discovery—Learning from the Past for the Future. Journal of Medicinal Chemistry, 66(9), 5377–5396. https://doi.org/10.1021/acs.jmedchem.3c00134

  • GlobalRPH. (2025). Emerging and Approved Therapeutic Peptides: Mechanisms, Clinical Uses. GlobalRPH.

  • Zhang, J., Zhou, Y., Zhu, T., & Zhu, Z. (2025). PepCCD: A Contrastive Conditioned Diffusion Framework for Target-Specific Peptide Generation. bioRxiv. https://doi.org/10.1101/2025.09.01.673427