[Leu27]-Melan-A, MART-1 (26-35)

Product Name: [Leu27]-Melan-A, MART-1 (26-35)

Sequence One Letter Code: ELAGIGILTV

Sequence Three Letter Code: H-Glu-Leu-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val-OH

Chemical Formula:C45H80N10O14

Molecular Weight: 985.3

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Cancer Immunotherapy

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: [Leu²⁷]-Melan-A (26–35) is a modified decapeptide analog of the native Melan-A tumor antigen in which alanine at position 27 is substituted with leucine, resulting in significantly enhanced binding affinity to HLA-A*0201 and improved peptide–MHC complex stability. This single amino acid modification increases antigenicity and immunogenicity compared with the native sequence, promoting stronger CD8⁺ T cell activation. The peptide is widely employed in tumor immunology and cancer vaccine research to investigate antigen presentation, T cell priming, and melanoma-specific cellular immune responses.

Current Research: [Leu²⁷]-Melan-A (26–35) is a heteroclitic decapeptide analog of the native Melan-A/MART-1 tumor-associated antigen epitope. In this modified sequence, alanine at position 27 is replaced with leucine, a substitution that markedly enhances binding affinity to HLA-A*0201 and improves peptide–MHC class I complex stability. This single anchor residue modification increases antigenicity while preserving T cell receptor (TCR) recognition of the native tumor epitope. Because of its superior HLA-A2 binding characteristics, [Leu²⁷]-Melan-A (26–35) has become one of the most widely utilized model epitopes in melanoma immunotherapy research, cancer vaccine development, and CD8⁺ T cell functional studies. Molecular Rationale for the Leu²⁷ Substitution The native Melan-A (26–35) peptide binds HLA-A*0201 with moderate affinity due to suboptimal anchor residue interactions. Position 2 of HLA-A2–restricted peptides is a primary anchor site, and substitution with leucine—an amino acid favored at this position—enhances: Peptide–HLA binding affinity Stability of the peptide–MHC complex Surface presentation density on antigen-presenting cells Importantly, the substitution does not substantially alter the TCR-facing residues, allowing many Melan-A–specific CD8⁺ T cells to cross-recognize both the analog and the native epitope. Enhanced Immunogenicity and T Cell Activation Compared with the native sequence, the [Leu²⁷] analog: Induces stronger CD8⁺ T cell priming in vitro Promotes higher cytokine production (e.g., IFN-γ, TNF-α) Enhances proliferation of antigen-specific T cells Improves functional avidity in some experimental systems These properties make it particularly useful for expanding Melan-A–specific T cells from peripheral blood or for evaluating vaccine-induced responses in HLA-A2–positive donors. Applications in Tumor Immunology 1. Cancer Vaccine Research [Leu²⁷]-Melan-A (26–35) has been incorporated into peptide-based vaccine platforms due to its improved MHC stability and immunogenicity. It serves as a model antigen for evaluating adjuvant systems, delivery vehicles, and T cell priming efficiency. 2. Immune Monitoring in Clinical Studies In melanoma clinical trials, the analog peptide is frequently used in: IFN-γ ELISPOT assays Intracellular cytokine staining (ICS) HLA-A2/MART-1 multimer staining CTL cytotoxicity assays Its enhanced stability often yields stronger assay signals compared to the native peptide, improving detection sensitivity. 3. T Cell Engineering and Adoptive Cell Therapy The peptide is commonly used to validate TCR-transduced T cells targeting MART-1. It enables assessment of activation thresholds, cytolytic function, and potential cross-reactivity between analog-primed T cells and tumor cells expressing the native antigen. Native vs. Heteroclitic Epitope Considerations While the [Leu²⁷] analog provides stronger in vitro expansion and activation, researchers must consider potential differences in TCR repertoire selection and functional avidity relative to the native tumor epitope. For translational studies, it is often advisable to confirm that T cells primed with the analog retain effective recognition of melanoma cells presenting endogenous Melan-A. Experimental Considerations Optimal peptide concentrations should be empirically determined based on assay format and cell type. In comparative studies, parallel testing with the native Melan-A (26–35) peptide can clarify functional differences in T cell activation and cross-reactivity.