Fmoc-Sar-OH.H2O

Fmoc-Sar-OH.H2O is an indispensable building block for Fmoc solid‑phase peptide synthesis requiring the incorporation of N‑alkylated amino acids. Fmoc-Sar-OH.H2O is a glycine derivative where the nitrogen is methylated, which confers a unique set of properties when incorporated into polypeptides. Fmoc-Sar-OH.H2O introduces flexibility in the peptide backbone — sarcosine has long been used in the design of peptoid‑peptide hybrids and as a solubilizing spacer in peptide–drug conjugates. Fmoc-Sar-OH.H2O is also used extensively in the construction of collagen‑mimetic sequences, where sarcosine’s ability to adopt specific backbone conformations contributes to triple‑helix stability. The monohydrate form is a stable, free‑flowing crystalline powder that is significantly easier to handle and weigh than the anhydrous form, and the water of hydration is typically removed during the initial stages of peptide assembly when the building block is dissolved in polar aprotic solvents (DMF or NMP). Additionally, the sarcosine residue is frequently employed as a flexible linker in peptide–drug conjugates and bifunctional molecules, where its lack of hydrogen‑bond donors reduces nonspecific interactions and improves pharmacokinetic properties.

Product Parameters

Synthetic Route

For Fmoc-Sar-OH.H2O, the synthetic preparation proceeds through the protection of sarcosine (N‑methylglycine) with the Fmoc group, followed by crystallization as the monohydrate. The general route involves:

(1) Sarcosine as starting material: Sarcosine (N‑methylglycine) is a commercially available N‑alkylated amino acid. The compound exists as a zwitterion in the solid state, with the secondary amine protonated and the carboxylate deprotonated.

(2) Fmoc protection: The secondary amine of sarcosine is reacted with Fmoc‑chloride (Fmoc‑Cl) or Fmoc‑OSu in the presence of a mild base (e.g., NaHCO₃ or Na₂CO₃) in an aqueous‑organic solvent system. The reaction proceeds via formation of a carbamate linkage between the Fmoc group and the sarcosine amine, yielding Fmoc‑sarcosine.

(3) Acidification and extraction: After completion of the protection reaction, the mixture is acidified to protonate the carboxyl group, and the product is extracted into an organic solvent (e.g., ethyl acetate or DCM).

(4) Crystallization as monohydrate: The crude Fmoc‑sarcosine is purified by recrystallization from an appropriate solvent system (typically water‑containing organic solvents) to yield Fmoc-Sar-OH.H2O as the crystalline monohydrate form.

Application Scenarios

1. Peptide–Drug Conjugate (PDC) Linker Synthesis

Sarcosine residues are increasingly employed as flexible, non‑immunogenic linkers in peptide–drug conjugates. The N‑methyl group eliminates hydrogen‑bond donors on the backbone amide, reducing nonspecific interactions and potentially enhancing pharmacokinetic properties. Fmoc-Sar-OH.H2O enables the assembly of PDCs with tunable linker properties via standard Fmoc‑SPPS.

2. Collagen‑Mimetic Peptide Design

Sarcosine is frequently used in the construction of collagen‑mimetic sequences, where its ability to adopt specific backbone conformations contributes to the stability of the collagen triple‑helix. Fmoc-Sar-OH.H2O is the protected building block needed for stepwise assembly of these structurally defined synthetic collagens.

3. Peptoid–Peptide Hybrid Synthesis

As an N‑alkylated amino acid, sarcosine bridges the gap between standard peptides (α‑amino acids) and peptoids (N‑substituted glycines). Fmoc-Sar-OH.H2O enables the synthesis of hybrid sequences that combine the structural diversity of peptoids with the established biological activity of peptide sequences.

4. Flexible Spacers in Bifunctional Molecules

The sarcosine residue (—Sar—) is widely used as a flexible, non‑cleavable spacer in bifunctional molecules — including PROTACs (proteolysis targeting chimeras), molecular glues, and imaging probes. The N‑methyl group prevents secondary structure formation and reduces nonspecific binding, providing a “stealth” linker.

5. Solubilizing “Helper” Residue in Hydrophobic Peptides

Sarcosine residues can be incorporated into hydrophobic peptide sequences to improve overall solubility in aqueous buffers, facilitating purification, formulation, and biological testing. The N‑methyl group reduces aggregation tendency without introducing charge or bulky side‑chains.

6. SPPS Method Development for N‑Alkylated Amino Acids

Peptide chemists developing new SPPS protocols for N‑alkylated amino acids — including novel coupling reagents, deprotection conditions, or protecting groups — use Fmoc-Sar-OH.H2O as the simplest model system for secondary amine coupling optimization.

7. Proteomics and Structure‑Activity Relationship Studies

Fmoc-Sar-OH.H2O is a standard building block for proteomics studies requiring the incorporation of modified amino acids into peptide sequences. Its unique properties make it a valuable tool for designing peptides with unique structural and functional motifs for advanced biochemical research.

8. Manufacture of Peptide Therapeutics with Improved Pharmacokinetics

For pharmaceutical companies developing peptide therapeutics, the incorporation of sarcosine residues can improve stability against proteolytic degradation (peptidases that cleave at primary amines are often less active against N‑alkylated amides), reduce immunogenicity, and enhance plasma half‑life.

Product Quality Assurance

Cosperpharm has established a comprehensive quality assurance system for Fmoc-Sar-OH.H2O that meets the rigorous expectations of both peptide synthesis building block supply and analytical reference standard applications:

Thorough analytical characterization. Each batch undergoes multi‑technique analytical release testing: HPLC purity (≥95.0% reference standard grade; ≥98.0% process grade, with full chromatographic traceability), melting point verification (for identity confirmation), appearance verification (white to off‑white powder), water content determination (Karl Fischer to confirm monohydrate stoichiometry), and identity confirmation by mass spectrometry.

Full batch traceability with retention samples. From raw material procurement (sarcosine from qualified suppliers) through Fmoc protection, purification, crystallization, drying, and final packaging, every step is fully documented and traceable. Each batch receives a unique lot number with sufficient retention samples maintained in accordance with Cosperpharm quality procedures.

Stability monitoring program. Cosperpharm conducts ongoing stability studies under recommended storage conditions: long‑term stability at –20 °C under inert atmosphere, with accelerated stability studies (40 °C / 75% RH) conducted on representative batches. Stability summaries are updated regularly, with full data packages available to support customer process validation and regulatory submissions.

Documentation ready for regulatory submission. Every shipment includes a Certificate of Analysis (COA) with batch‑specific purity and characterization data, a Material Safety Data Sheet (SDS), and customs documentation for international delivery. For customers preparing validated SPPS processes for peptide therapeutics or filing regulatory submissions, Cosperpharm provides DMF‑ready documentation packages, stability data, and custom quality agreements upon request.

Customer‑initiated quality audits. Qualified customers are welcome to audit Cosperpharm‘s manufacturing, quality control, and documentation facilities. Please contact our regulatory team to schedule an audit. ISO compliance documentation is available upon request.

Contact us

From flexible linkers in peptide–drug conjugates to triple‑helical collagen mimetics, Fmoc-Sar-OH.H2O unlocks the unique conformational and solubility properties of N‑alkylated amino acids. Reach out to Cosperpharm today to request a quote or discuss your peptide synthesis requirements.