3,4-Dimethy-D-Phenylalanine is a non-proteinogenic, D-configured phenylalanine derivative bearing two methyl substituents at the 3 and 4 positions of the aromatic ring, classifying it as an aryl-substituted amino acid. The molecule contains a primary amino group and a carboxylic acid functional group on the α-carbon while the side chain presents a substituted benzyl aromatic moiety that can modulate hydrophobicity and steric interactions relative to unsubstituted phenylalanine. As an unnatural amino acid building block, it is used in peptide synthesis and structure-activity studies to introduce a defined ring-substitution pattern for studying how aromatic substitution affects peptide conformation, binding, and labeling chemistry.
CAT No: CP14202
3,4-Dimethy-D-Phenylalanine is a D-configured, non-proteinogenic phenylalanine analog featuring two methyl substituents on the aromatic ring, providing increased hydrophobicity and steric modulation relative to unsubstituted phenylalanine. This chiral, non-natural amino acid building block is commonly used in peptide and peptidomimetic design where aromatic side-chain shape and steric bulk are leveraged to probe structure-activity relationships and tune conformational preferences. Its stereodefined D-configuration makes it particularly valuable for workflows that require non-natural residue incorporation to alter peptide behavior without relying on proteinogenic amino acid identity.
1. Peptidomimetic SAR Studies
3,4-Dimethy-D-Phenylalanine is used by medicinal chemistry and chemical biology teams to build peptidomimetic libraries and structure-activity relationship (SAR) panels in which aromatic side-chain substitution patterns are systematically varied. The 3,4-dimethyl substitution on the phenyl ring provides a practical handle for studying how increased steric bulk and altered hydrophobic character affect binding-site complementarity, local conformational bias, and overall peptide-like scaffold performance. Researchers typically incorporate this residue into short, defined sequences (often as protected amino acid derivatives in custom peptide synthesis) to generate analog series for downstream biological screening and analog comparison, while the D-configuration supports the exploration of stereochemical effects on structure and function.
2. Protease Resistance Probing
3,4-Dimethy-D-Phenylalanine is frequently selected in peptide stability and degradation studies aimed at understanding how non-natural stereochemistry and side-chain substitution influence proteolytic processing of peptide scaffolds. In peptide engineering workflows, D-amino acid incorporation is used as a strategy to modulate enzymatic recognition and cleavage patterns, and the additional aromatic methyl substitution further changes the residue's steric environment within the peptide backbone context. This makes the building block useful for generating defined degradation substrates for in vitro stability experiments, protease panel testing, and comparative analyses of analogs that differ specifically at the aromatic residue position.
3. Conformational Control Inhibitor Design
3,4-Dimethy-D-Phenylalanine supports conformational control approaches in inhibitor and ligand design where aromatic side-chain geometry and steric profile are used to influence folding or local structure in peptide-like molecules. Medicinal chemistry groups incorporate this D-configured, 3,4-dimethyl aromatic residue into constrained or semi-flexible peptide frameworks to evaluate how side-chain bulk affects turn formation, helix/strand propensity, and intramolecular packing. The result is a practical building block for developing analogs used in lead optimization campaigns, where residue-level structural changes are introduced to refine physicochemical properties and improve the interpretability of structure-function relationships across a series of closely related compounds.
4. Non-Natural Residue Labeling Standards
3,4-Dimethy-D-Phenylalanine is also used in analytical and method-development contexts where defined non-natural amino acid content is required for calibration, reference material preparation, or compositional verification of peptide intermediates and final products. Because it is a distinct, non-proteinogenic D-amino acid with a uniquely substituted aromatic side chain, it can serve as a discriminating residue marker in workflows that distinguish engineered sequences from those containing only proteinogenic amino acids. Analytical chemists and peptide manufacturing development teams commonly employ it to support LC-MS method qualification, peptide characterization, and identity checks during process development for custom peptide synthesis and peptidomimetic manufacturing.
1. Immune responses to homocitrulline-and citrulline-containing peptides in rheumatoid arthritis
2. Myotropic activity of allatostatins in tenebrionid beetles
4. Implications of ligand-receptor binding kinetics on GLP-1R signalling
5. Low bone turnover and low BMD in Down syndrome: effect of intermittent PTH treatment
If you have any peptide synthesis requirement in mind, please do not hesitate to contact us at . We will endeavor to provide highly satisfying products and services.
Creative Peptides is a trusted CDMO partner specializing in high-quality peptide synthesis, conjugation, and manufacturing under strict cGMP compliance. With advanced technology platforms and a team of experienced scientists, we deliver tailored peptide solutions to support drug discovery, clinical development, and cosmetic innovation worldwide.
From custom peptide synthesis to complex peptide-drug conjugates, we provide flexible, end-to-end services designed to accelerate timelines and ensure regulatory excellence. Our commitment to quality, reliability, and innovation has made us a preferred partner across the pharmaceutical, biotechnology, and personal care industries.
Read More