4-tert-butyl-L-Phenylalanine is a non-natural, aromatic amino acid derivative classified within the phenylalanine family, featuring a benzyl side chain bearing a tert-butyl substituent at the para (4-) position relative to the benzylic carbon. The molecule contains a free amino group and a free carboxyl group and is specified as the L stereochemical form at the α-carbon, with the bulky hydrophobic tert-butyl substituent modulating side-chain sterics and aromatic character. It is used in peptide and protein engineering workflows and structure-activity studies as a substituted phenylalanine building block that can be incorporated into synthetic peptides to probe effects of altered side-chain shape, hydrophobicity, and aromatic substitution patterns.
CAT No: CP11301
CAS No:82372-74-5
Synonyms/Alias:82372-74-5;L-4-TERT-BUTYL-PHE;4-tert-Butyl-L-phenylalanine;(S)-2-Amino-3-(4-(tert-butyl)phenyl)propanoicacid;(2S)-2-amino-3-(4-tert-butylphenyl)propanoicacid;L-4-TBU-PHE-OH;AC1MC5RJ;H-P-TBU-PHE-OH;H-PHE(4-TBU)-OH;L-PHE(4-TBU)-OH;L-4-tert-butyl-phenylalanine;SCHEMBL383814;MolPort-001-758-817;L-4-TERT-BUTYLPHENYLALANINE;L-4-TETR-BUTYLPHENYLALANINE;ZINC2392305;P-TERT-BUTYL-L-PHENYLALANINE;4-(T-BUTYL)-L-PHENYLALANINE;KM2114;AKOS012010563;AB11722;AL389-1;AM82723;CB-1300;OR14740
4-tert-butyl-L-Phenylalanine is a sterically hindered, non-natural phenylalanine analog featuring a tert-butyl substituent on the aromatic ring, provided in the L-configuration for stereochemically defined peptide and medicinal chemistry work. Its bulky hydrophobic side chain makes it a useful building block for tuning aromatic packing, local conformational preferences, and physicochemical properties in larger molecules. Researchers commonly employ this amino acid in peptide drug discovery and structure-property studies where aromatic substitution patterns need to be represented with a defined stereocenter.
1. Peptide Drug Discovery
4-tert-butyl-L-Phenylalanine is used as a non-natural amino acid building block in peptide synthesis workflows to introduce a highly substituted, hydrophobic aromatic side chain at specific positions. Medicinal chemistry teams incorporate it into peptide leads and peptidomimetic scaffolds to probe how increased steric bulk and altered aromatic surface area influence overall structure, aggregation tendency, and developability-related properties. Because it is supplied as the L-enantiomer, it is also favored when stereodefined analog series are required for SAR (structure-activity relationship) studies and for comparing position-specific effects across peptide variants.
2. Structure-Activity Relationship Studies
4-tert-butyl-L-Phenylalanine supports SAR and conformational investigation efforts by providing a defined aromatic substitution pattern that differs from unsubstituted phenylalanine. Chemical biology and medicinal chemistry groups use it to systematically vary side-chain sterics and hydrophobic character within analog libraries, enabling clearer interpretation of how aromatic ring substitution impacts binding-site complementarity and target interaction geometry in peptide-based systems. This amino acid is particularly relevant when researchers need a stable, synthetically accessible way to encode "bulky phenyl" character into a defined residue for downstream biological characterization.
3. Peptidomimetic Scaffold Optimization
4-tert-butyl-L-Phenylalanine is frequently selected for peptidomimetic and constrained scaffold development where aromatic side-chain shape and steric footprint are key design variables. R&D teams use it to improve the chemical realism of peptide-like inhibitors and receptor-binding motifs by replacing standard aromatic residues with a tert-butyl-substituted analog that can better represent hydrophobic pocket occupancy and steric shielding effects. In practical development pipelines, this residue is also used to create analog panels that help refine lead series by correlating structural changes at the residue level with observed trends in assay readouts and developability metrics.
4. Pharmaceutical Intermediate Development
4-tert-butyl-L-Phenylalanine is used as a stereochemically defined intermediate for downstream synthesis of substituted aromatic amino acid derivatives and related building blocks used in medicinal chemistry programs. Process and synthesis teams incorporate it into routes that require a bulky, hydrophobic phenylalanine motif to be carried through as a protected or activated intermediate toward larger coupling partners. This makes it valuable for preparing defined analogs for library generation, custom peptide synthesis, and specialty intermediate manufacturing where the tert-butyl-substituted aromatic side chain must be preserved with L-configuration throughout the synthetic sequence.
2. C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy
5. Adipose tissue is a key organ for the beneficial effects of GLP-2 metabolic function
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