Peptide Linkers

Peptide linkers play a crucial role in bioconjugation, protein engineering, and drug development. These short peptide chains connect functional units within or between biomolecules. Their design directly affects the stability, function, and effectiveness of products like fusion proteins and antibody-drug conjugates (ADCs).

Why Peptide Linkers Matter:

1. Add Flexibility: They allow connected components to move freely, ensuring proteins or conjugates maintain their activity.
2. Prevent Interference: Acting as spacers, they reduce steric hindrance between functional groups, enabling smoother performance.
3. Boost Stability and Solubility: Proper linkers enhance solubility and stability, preventing unwanted aggregation.
4. Enable Controlled Release: Cleavable linkers release drugs or other payloads at target sites under specific conditions, like enzyme action or pH changes.
5. Improve Drug Targeting: In ADCs, they ensure the drug reaches its target without disrupting the antibody’s binding ability.

Types of Peptide Linkers:

• Flexible Linkers: Made from amino acids like glycine and serine, these provide free movement between domains (e.g., (Gly₄Ser)₂).
• Rigid Linkers: These include alpha-helices or beta-sheets that keep domains in a fixed orientation.
• Cleavable Linkers: Designed to break under certain conditions, they control drug release (e.g., Val-Cit, Gly-Phe-Leu-Gly).
• Non-Cleavable Linkers: These form permanent, stable connections.
• PEG-Peptide Linkers: Combining PEG with peptides, they offer better solubility and controlled connections, commonly used in ADCs.

Peptide linkers are vital tools in modern biochemistry and drug development. They offer flexibility, stability, and control, making them key components in advancing therapeutics and research. Ref: Liming Gong, Heming Zhao, Yanhong Liu, Hao Wu, Chao Liu, Shuangyan Chang, Liqing Chen, Mingji Jin, Qiming Wang, Zhonggao Gao, Wei Huang, Research advances in peptide‒drug conjugates, Acta Pharmaceutica Sinica B, Volume 13, Issue 9, 2023, Pages 3659-3677. AxisPharm has a large collection of peptide linkers, PEG peptide linkers, and PEGylated peptide synthesis reagents in stock. Custom syntheses of peptide PEG are available upon request.