Fmoc-Tle-OH

Fmoc-Tle-OH (Fmoc‑L‑tert‑leucine) is a specialized Fmoc‑protected amino acid building block widely utilized in research focused on peptide synthesis and drug development. Fmoc-Tle-OH features a bulky tert‑butyl side chain that introduces steric hindrance into peptide sequences, effectively restricting conformational flexibility and enhancing proteolytic stability. Fmoc-Tle-OH is particularly valuable in the design of bioactive peptides and peptidomimetics where spatial pre‑organization is critical for target engagement, including the development of XIAP antagonists for cancer treatment and bioactive peptides for neurodegenerative diseases. Fmoc-Tle-OH has also demonstrated promising results in the treatment of prostate cancer, where it has been shown to be effective against resistant prostate cancer cells in vivo and inhibits the growth of prostate cancer cells in vitro.

Product Parameters

Product Advantages

1. Bulky tert‑butyl side chain for steric hindrance. The tert‑butyl group (‑C(CH₃)₃) imposes significant steric congestion around the α‑carbon, restricting backbone conformational flexibility and favoring β‑turn and helical secondary structures. This property is essential for designing peptides with defined three‑dimensional architectures and enhanced target selectivity.

2. Orthogonal Fmoc protection for standard SPPS. The Fmoc protecting group is base‑labile and orthogonal to acid‑sensitive side‑chain protections, enabling seamless integration into standard Fmoc solid‑phase peptide synthesis workflows. Deprotection proceeds efficiently under mild piperidine conditions.

3. Enhanced proteolytic stability. Incorporation of L‑tert‑leucine into peptide sequences dramatically improves resistance to proteolytic degradation by endo‑ and exopeptidases. The bulky side chain shields adjacent amide bonds from enzymatic recognition and cleavage, extending the plasma half‑life of peptide therapeutics.

4. Valuable for XIAP antagonist development. Fmoc-Tle-OH is a versatile reactant used in the discovery of potent antagonists of the antiapoptotic protein X‑linked inhibitor of apoptosis (XIAP) for the treatment of cancer, particularly prostate cancer. The bulky tert‑butyl group is critical for occupying the hydrophobic binding pocket of XIAP.

5. Enhances solubility and reduces aggregation. The hydrophobic tert‑butyl side chain can improve the solubility of certain peptide sequences in organic solvents and reduce chain aggregation during Fmoc‑SPPS, particularly for difficult sequences prone to β‑sheet formation.

6. Promising results in prostate cancer research. Fmoc‑L‑tert‑leucine has been shown to be effective in treating resistant prostate cancer cells in vivo and has been demonstrated to inhibit the growth of prostate cancer cells in vitro, with diagnostic applications for prostate cancer cell detection.

Synthetic Route

The general procedure for synthesizing Fmoc-L-tert-lysine from L-tert-lysine and 9-fluoromethyl chloroformate is as follows: In a 500 mL reaction flask, add L-tert-lysine (5.1 g, 38.6 mmol), dioxane (40 mL), and a 10% sodium carbonate solution (100 mL). Place the flask in an ice bath and, under mechanical stirring, slowly add the dioxane solution of 9-fluoromethyl chloroformate (10.0 g, 38.6 mmol) via a dropping funnel. After completion of addition, gradually return to room temperature and continue stirring overnight. Upon reaction completion, add 100 mL water and extract three times with 50 mL of ethyl ether; retain the aqueous phases. Cool the aqueous phase in an ice bath, then slowly add 1 M dilute hydrochloric acid to adjust the pH to 1. Subsequently, extract the aqueous solution three times with 50 mL of ethyl acetate. Combine the organic phases, dry with anhydrous magnesium sulfate, filter, and concentrate until dry to obtain the intermediate Fmoc-L-tert-lysine (14.3 g, yield 96%).

FAQ

Q1: What are the primary pharmaceutical applications of Fmoc-Tle-OH?

A: Fmoc-Tle-OH is widely used in the development of pharmaceuticals and bioactive peptides, including: XIAP (X‑linked inhibitor of apoptosis) antagonists for cancer treatment, protease‑resistant therapeutic peptides, constrained peptide ligands for intracellular targets, and peptidomimetics for neurodegenerative diseases.

Storage Conditions

Store Fmoc-Tle-OH in a tightly sealed container at 2–8 °C for short‑term storage, protected from light and moisture. For long‑term storage (>12 months), store at –20 °C under inert atmosphere (nitrogen or argon) in a desiccated environment. The compound should be allowed to reach ambient temperature before opening the container to minimize moisture condensation. Keep away from strong oxidizing agents, strong bases, and sources of ignition.

Shelf life: 3 years when stored at –20 °C in a sealed container under inert atmosphere; 2 years when stored at 4 °C. For stock solutions in DMSO or DMF, store in single‑use aliquots at –80 °C (6 months stability) or –20 °C (1 month stability) to avoid degradation from repeated freeze‑thaw cycles.

Handling precautions: Use in a fume hood. Wear chemical‑resistant gloves (tested against EN 374 or equivalent), safety goggles, and a lab coat. Avoid generating dust or aerosols. Do not eat, drink, or smoke in work areas. After handling, wash hands thoroughly. Refer to the Safety Data Sheet (SDS) for complete safety information.

Contact Us

Whether you are designing a novel peptide therapeutic, developing XIAP antagonists for oncology, or scaling up a GMP peptide manufacturing process, Cosperpharm delivers Fmoc-Tle-OH with the purity, documentation, and supply reliability you need. Contact us today for a competitive quote or to discuss your specific requirements.