Fmoc-N-Me-Cys(Trt)-OH (CAS 944283-16-3): Advanced SPPS Reagent & Technical Guide

In modern solid-phase peptide synthesis (SPPS), chemical biology, and peptidomimetic engineering, controlling peptide backbone conformation, disulfide bond formation, and enzymatic stability represents a primary design goal. Incorporating NαN^\alphaNα-methylated amino acid derivatives allows synthetic chemists to eliminate amide hydrogen-bond donors, disrupt interchain self-assembly, and improve biological half-life. Among these specialized reagents, Fmoc-N-Me-Cys(Trt)-OH (CAS 944283-16-3) serves as an essential orthogonal building block for introducing backbone-modified cysteine residues into complex cyclic and linear peptide sequences.

Cysteine contains a highly reactive thiol side chain susceptible to premature oxidation, racemizaton, and unwanted cross-linking if unshielded during synthesis cycles. For research facilities seeking to evaluate Fmoc-N-Me-Cys(Trt)-OH CAS 944283-16-3 price structures and secure a validated buy Fmoc-N-Me-Cys(Trt)-OH supplier, acquiring analytical-grade reagents from amino asylum ensures high coupling efficiency, structural fidelity, and reproducible batch-to-batch performance.

What is Fmoc-N-Me-Cys(Trt)-OH (Fmoc-N-methyl-L-cysteine(Trt))?

Fmoc-N-Me-Cys(Trt)-OH, chemically designated as NαN^\alphaNα-(((9H-fluoren-9-yl)methoxy)carbonyl)-NαN^\alphaNα-methyl-$S$-trityl-$L$-cysteine, is an NαN^\alphaNα-methylated, side-chain protected amino acid derivative engineered specifically for standard Fmoc/tBu SPPS protocols.

Substituting a methyl group onto the $\alpha$-amino nitrogen converts a standard secondary amide linkage into a tertiary amide within the peptide backbone. This modification alters local steric parameters, removes a hydrogen-bond donor site, and shifts the cis/trans amide bond equilibrium toward defined secondary structures.

                 [ Fmoc-N-Me-Cys(Trt)-OH Chemical Architecture ]
                                        │
        ┌───────────────────────────────┼───────────────────────────────┐
        ▼                               ▼                               ▼
[ Base-Labile Fmoc ]           [ N-Methylated Nitrogen ]       [ Acid-Labile S-Trt Shield ]
(Alpha-Amine Protection)       (Eliminates H-Bond Donor)       (Thiol Side-Chain Protection)
        │                               │                               │
        ▼                               ▼                               ▼
 Deprotects via 20%             Prevents Beta-Sheets &          Prevents Disulfide Dimerization
 Piperidine in DMF              Resin Aggregation               & Thiol Oxidation

Molecular Architecture & Chemical Identity of CAS 944283-16-3

The chemical parameters of CAS 944283-16-3 define its utility as a core building block for custom peptide modification:

Chemical Specifications Reference:
• Full Chemical Name: N-alpha-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-alpha-methyl-S-trityl-L-cysteine
• CAS Registry Number: 944283-16-3
• Common Nomenclature: Fmoc-N-methyl-L-cysteine(Trt)
• Abbreviated Name: Fmoc-N-Me-Cys(Trt)-OH / Fmoc-MeCys(Trt)-OH
• Molecular Formula: C38H33NO4S
• Molecular Weight: 599.74 g/mol
• Protect Group Matrix: N-alpha (Fmoc, base-labile), Thiol S-atom (Trityl/Trt, acid-labile)
• Physical State: Off-white to white powder
• Storage Parameters: Refrigerated (-20°C to 4°C), desiccated, sheltered from light

Dual Orthogonal Protection: Fmoc and Trityl (Trt) Thiol Shielding

Base-Labile N-alpha Fmoc Deprotection Dynamics

The 9-Fluorenylmethyloxycarbonyl (Fmoc) group protects the NαN^\alphaNα-methylated amine during storage and coupling steps. Deprotection proceeds efficiently via base-catalyzed $E1cB$ elimination using $20\%$ piperidine in DMF, yielding a secondary NαN^\alphaNα-methylamine ready for subsequent elongation cycles without affecting acid-sensitive side-chain protecting groups.

Acid-Labile Side-Chain S-Trityl Protection and Suppression of Oxidative Dimerization

The reactive thiol group on the cysteine $\beta$-carbon is shielded by a bulky Triphenylmethyl (Trityl / Trt) group. This bulky protecting group prevents premature disulfide bond formation, oxidation to cysteic acid, or $\beta$-elimination side reactions during basic deprotection steps. The $S$-Trt group remains intact during base deprotection steps and is removed during trifluoroacetic acid (TFA) cleavage or selective iodine-mediated oxidation for direct disulfide pairing.

Applications of Fmoc-N-methyl-L-cysteine(Trt) Bulk Manufacturer Reagents in SPPS

                            [ SPPS Assembly Kinetics ]
                                        │
        ┌───────────────────────────────┴───────────────────────────────┐
        ▼                                                               ▼
[ Unmodified Sequence Assembly ]                             [ N-Methylated Insertion ]
        │                                                               │
        ▼                                                               ▼
[ Interchain H-Bonded Beta-Sheets ]                          [ Steric Backbone Disruption ]
        │                                                               │
        ▼                                                               ▼
[ Premature Termination / Low Yield ]                        [ Solvated Resin / High Coupling Yield ]

Backbone Methylation and Elimination of Beta-Sheet Self-Assembly

During long-chain SPPS, peptide chains often establish interchain hydrogen bonds between backbone amide protons ($\text{-NH-}$) and carbonyl oxygens ($\text{-C=O}$). This interaction can cause hydrophobic $\beta$-sheet aggregation on the resin support, shrinking resin matrix pores and limiting reagent access to the terminal amine.

Utilizing building blocks sourced from a verified Fmoc-N-methyl-L-cysteine(Trt) bulk manufacturer removes the amide hydrogen at the target locus. Inserting Fmoc-N-Me-Cys(Trt)-OH breaks up local $\beta$-sheet secondary structures, preserving resin swelling and improving step-wise coupling yields in difficult sequences.

Disulfide Bridge Engineering and Proteolytic Resistance in Cyclic Peptides

NαN^\alphaNα-methylated cysteine residues offer significant structural advantages in cyclic peptide design:

• Conformational Constraint: Placing an NαN^\alphaNα-methyl group on a cysteine residue stabilizes specific loop conformations prior to disulfide formation, optimizing oxidation kinetics.

• Enzymatic Shielding: The NαN^\alphaNα-methyl group sterically blocks cleavage by serum endopeptidases and exopeptidases, increasing compound half-life in biological assays.

Synthetic Protocols & Chemistry: How to Synthesize Fmoc-N-Me-Cys(Trt)-OH

Synthetic Routes for N-Methylation of S-Protected Cysteine Derivatives

Understanding how to synthesize Fmoc-N-Me-Cys(Trt)-OH involves examining specialized NαN^\alphaNα-methylation methods designed to prevent racemization of the sensitive $\alpha$-carbon:

Synthetic Route Overview:
1. S-Protection: L-Cysteine is reacted with Trityl chloride (Trt-Cl) in TFA/DMF to yield H-Cys(Trt)-OH.
2. N-Fmoc Protection: H-Cys(Trt)-OH is reacted with Fmoc-OSu under basic conditions to yield Fmoc-Cys(Trt)-OH.
3. Oxazolidinone Formation: Fmoc-Cys(Trt)-OH is reacted with paraformaldehyde under acid catalysis to form a cyclic 5-oxazolidinone intermediate.
4. Silane Reduction: Triethylsilane (TES) and TFA selectively open the oxazolidinone ring, yielding the pure N-methylated derivative Fmoc-N-Me-Cys(Trt)-OH without enolization or chiral loss.

Coupling Procedures, Racemization Control, and TFA Cleavage Protocols

When coupling onto or extending past a sterically hindered Fmoc-N-methyl-L-cysteine(Trt) residue, activation conditions must be strictly controlled:

• Primary Activation System: HATU (5 eq) / HOAt (5 eq) or COMU (5 eq) with DIPEA (10 eq).

• Alternative Activation: DIC (5 eq) / Oxyma Pure (5 eq) to suppress $\alpha$-carbon racemization during coupling.

• TFA Cleavage & Scavenger System: TFA/TIS/EDT/H2O\text{TFA} / \text{TIS} / \text{EDT} / \text{H}_2\text{O}TFA/TIS/EDT/H2​O ($92.5:2.5:2.5:2.5\text{ v/v/v/v}$). Ethanedithiol ($\text{EDT}$) or triisopropylsilane ($\text{TIS}$) traps liberated trityl cations, preventing re-attachment to the free thiol.

Comparative Analysis & Catalog Integration

Comparing N-Methyl Cysteine Building Blocks with Fmoc-N-Me-His(Trt)-OH and Protected Derivatives

Integrating Fmoc-N-Me-Cys(Trt)-OH alongside other NαN^\alphaNα-methylated derivatives—such as Fmoc-N-Me-His(Trt)-OH—provides synthetic chemists with a functional toolset to modify both thiol-containing and basic positions within target peptide sequences.

                      [ Reagent Sourcing to Finished Research ]
                                         │
     ┌───────────────────────────────────┼───────────────────────────────────┐
     ▼                                   ▼                                   ▼
[ Chemical Synthesis Blocks ]   [ Stabilized Neuropeptides ]        [ Metabolic & Repair Compounds ]
 • Fmoc-N-Me-Cys(Trt)-OH        • N-Acetyl-Semax Spray              • Buy Noopept
 • Fmoc-N-Me-His(Trt)-OH        • N-Acetyl-Selank Spray             • NAD+ Spray
                                • PT-141 Spray / MT-II Spray        • glutathione spray
                                                                    • BPC-157 Spray / AOD-9604 Spray

From Chemical Building Blocks to Bioactive Formulations

Laboratory workflows bridge raw reagent synthesis and post-synthesis empirical research. Chemical strategies evaluated during solid-phase assembly directly inform research on finished reference products:

• Cognitive & Nootropic Protocols: Custom peptide synthesis data complement evaluations of established central dipeptides like Buy Noopept.

• Cellular Bioenergetics & Redox: Synthetic design projects frequently run alongside investigations into cellular energy catalysts like NAD+ Spray and endogenous antioxidants like glutathione spray.

• Tissue Repair & Metabolic Signaling: Advanced peptide research pairs custom-synthesized chains with functional reference compounds like BPC-157 Spray and lipolytic fragments such as AOD-9604 Spray.

• Melanocortin & Neuropeptide Pathways: Structural stabilization techniques mirror protocols used in specialized research products, including melanocortin agonists like PT-141 Spray and MT-II Spray, as well as stabilized intranasal neuropeptides like N-Acetyl-Semax Spray and N-Acetyl-Selank Spray.

Sourcing Reagents: Where to Buy Fmoc-N-Me-Cys(Trt)-OH for Peptide Synthesis

When determining where to buy Fmoc-N-Me-Cys(Trt)-OH for peptide synthesis, procurement managers evaluate analytical purity, batch consistency, and supplier verification.

Evaluating Fmoc-N-Me-Cys(Trt)-OH CAS 944283-16-3 Price and Quality Standards

Reagent purity directly impacts crude peptide assembly quality and downstream purification workloads. Every batch of Fmoc-N-Me-Cys(Trt)-OH (CAS 944283-16-3) supplied by Amino Asylum undergoes full analytical quality testing:

• High-Performance Liquid Chromatography (HPLC): Confirms chemical purity ($\ge 98.0\%$).

• Proton Nuclear Magnetic Resonance (1H-NMR^1\text{H-NMR}1H-NMR): Verifies correct structural assignment of the Fmoc group, NαN^\alphaNα-methyl group, and side-chain $S$-Trt protecting group without unassigned impurities.

• Mass Spectrometry (MS): Validates precise molecular weight ($599.74\text{ g/mol}$).

Selecting a Reliable Buy Fmoc-N-Me-Cys(Trt)-OH Supplier at Amino Asylum

Laboratories securing reagents through a verified buy Fmoc-N-Me-Cys(Trt)-OH supplier like amino asylum receive high-purity, batch-tested synthesis building blocks backed by analytical documentation and reliable fulfillment.

Frequently Asked Questions (FAQ)

What Is the Full Chemical Name for Fmoc-N-methyl-L-cysteine(Trt)?

The full chemical name is NαN^\alphaNα-(((9H-fluoren-9-yl)methoxy)carbonyl)-NαN^\alphaNα-methyl-$S$-trityl-$L$-cysteine, indexed under CAS 944283-16-3 and abbreviated as Fmoc-N-Me-Cys(Trt)-OH or Fmoc-MeCys(Trt)-OH.

Why Is Side-Chain S-Trityl Protection Vital During Fmoc Deprotection Steps?

The steric bulk and stability of the $S$-Triphenylmethyl ($\text{Trt}$) group prevents base-catalyzed oxidation, thiol-disulfide exchange, or $\beta$-elimination side reactions during repeated piperidine treatments.

How Does N-Methyl Cysteine Prevent Racemization During Activation Steps?

While cysteine is normally prone to racemization via base-catalyzed $\alpha$-proton abstraction, the presence of the NαN^\alphaNα-methyl substituent combined with optimized activation reagents (such as DIC/Oxyma) significantly stabilizes the chiral center during carboxyl activation.

Final Verdict: Sourcing High-Purity Fmoc-N-Me-Cys(Trt)-OH for Research

Optimizing peptide assembly, overcoming secondary aggregation, and engineering backbone stability require analytical-grade chemical building blocks. Fmoc-N-Me-Cys(Trt)-OH (CAS 944283-16-3) provides the structural control necessary for incorporating protected NαN^\alphaNα-methylated cysteine residues into custom SPPS sequences.

When evaluating Fmoc-N-Me-Cys(Trt)-OH CAS 944283-16-3 price options or selecting a verified supplier for your laboratory, amino asylum delivers batch-verified purity, detailed analytical documentation, and consistent fulfillment to support your custom synthesis protocols.