|
HYD1 is a short, bioactive synthetic peptide with the sequence KIKMVISWKG, originally identified through combinatorial peptide library screening as a functional antagonist of a4b1 integrin (VLA-4). Unlike classical integrin ligands that mimic extracellular matrix motifs, HYD1 interacts with integrins through a non-RGD mechanism, leading to unique biological effects that have been widely studied in cancer biology, cell adhesion, and apoptosis research.
Molecular and Structural Features
HYD1 is a 10-amino-acid peptide enriched in basic residues (lysine and arginine), contributing to its strong interaction with cell surface proteins and integrin complexes. Its compact size allows efficient synthesis, high purity, and facile chemical modification for downstream applications such as labeling or conjugation. Importantly, HYD1 does not structurally resemble native integrin ligands, which explains its atypical mode of action and selective biological effects.
Functional Roles and Mechanism of Action
Extensive peer-reviewed studies have demonstrated that HYD1 disrupts a4b1 integrin–mediated cell adhesion, particularly in hematological malignancies. In multiple myeloma models, HYD1 induces detachment-associated apoptosis (anoikis-like cell death) rather than simple adhesion blockade. Mechanistic investigations revealed that HYD1 triggers necrotic or non-apoptotic cell death pathways, including mitochondrial dysfunction, ATP depletion, and reactive oxygen species (ROS) generation.
Unlike many integrin antagonists, HYD1 selectively targets malignant cells while showing minimal toxicity toward normal hematopoietic cells, making it a valuable research tool for studying integrin-dependent survival signaling. These properties have positioned HYD1 as a prototype peptide for investigating integrin-mediated drug resistance and tumor–microenvironment interactions.
HYD1 has been widely used in:
- Cancer research, particularly multiple myeloma and leukemia models
- Cell adhesion and migration assays involving a4b1 integrin
- Studies of integrin-mediated survival signaling and anoikis resistance
- Combination therapy research, where HYD1 enhances the cytotoxicity of chemotherapeutic agents by disrupting protective cell–matrix interactions
- Its reproducible activity and well-documented mechanism make HYD1 an excellent positive control or mechanistic probe in integrin biology studies.
Peer-reviewed publications suggest that HYD1 serves as a promising lead compound for developing next-generation integrin-targeting therapeutics. While HYD1 itself is primarily used as a research reagent, its unique mode of inducing tumor-selective cell death continues to inform the design of novel peptidomimetics and integrin-directed strategies aimed at overcoming microenvironment-mediated drug resistance.
HYD1 (KIKMVISWKG) is a well-characterized integrin-modulating peptide with a strong foundation in peer-reviewed literature. Its ability to disrupt a4b1 integrin–dependent adhesion and induce selective cancer cell death makes it a powerful tool for studying tumor biology, cell–matrix interactions, and therapeutic resistance mechanisms. HYD1 remains a valuable reagent for both fundamental research and translational studies exploring integrin-targeted interventions.
| 