Fmoc-α-Me-Lys(Boc)-OH is an Fmoc-protected, α-methylated L-lysine building block for the synthesis of conformationally constrained peptides and noncanonical peptide analogs. The α-amino group is protected by Fmoc, while the lysine ε-amino group is protected by Boc, allowing the residue to be used within conventional Fmoc/tBu solid-phase peptide synthesis workflows.

The defining feature is the methyl substituent on the α-carbon. This changes backbone steric demand and conformational preference without methylating the lysine side-chain nitrogen. For peptide SAR programs, α-methyllysine can therefore be used to test whether reduced local backbone flexibility improves target recognition, stability, or overall peptide behavior.

Product Information

What Does α-Methylation Change?

Replacing the normal α-hydrogen of lysine with a methyl group increases substitution around the peptide backbone. In a final peptide, that additional steric demand can restrict the conformational space accessible around the modified residue. The effect is sequence-dependent, so α-methylation is most useful as a deliberate SAR variable rather than as a universal stability modification.

We consider this distinction important when planning analog libraries: α-methyllysine changes backbone geometry, while retaining a lysine-like side chain after Boc removal. It is therefore chemically different from modifications that methylate the ε-amino group and directly alter side-chain charge, hydrogen bonding, or recognition.

Fmoc-α-Me-Lys(Boc)-OH vs Fmoc-Lys(Me,Boc)-OH

These names describe different molecules. In Fmoc-α-Me-Lys(Boc)-OH, the methyl group is attached to the α-carbon. In Fmoc-Lys(Me,Boc)-OH, methylation is associated with the lysine side-chain nitrogen. The distinction is easy to miss in abbreviated catalog names.

Both compounds can have the same molecular formula, C27H34N2O6, and the same nominal molecular weight, 482.57 g/mol. As a result, molecular mass alone does not establish which methyllysine isomer is present. For sequence-critical work, the CAS number, drawn structure, stereochemical assignment and lot-specific analytical documentation should be checked together.

Fmoc/Boc Protecting-Group Logic

Fmoc provides temporary protection of the α-amino group and is removed under the basic conditions normally used during Fmoc-SPPS. Boc protects the lysine ε-amino group during chain elongation and is typically removed during final acid-mediated cleavage and side-chain deprotection. This orthogonal arrangement prevents the lysine side-chain amine from competing in routine coupling reactions.

Coupling Considerations in SPPS

The α-methyl substituent increases steric congestion around the amino-acid backbone. Coupling can therefore be more demanding than with conventional Fmoc-Lys(Boc)-OH, particularly in sterically crowded or aggregation-prone sequences. Published peptide-synthesis routes using Fmoc-α-Me-Lys(Boc)-OH have employed DIC/Oxyma activation, increased reagent equivalents, repeated coupling, and reaction-completion monitoring when needed.

We recommend treating α-methyl residues as sequence-dependent difficult couplings. A stronger or longer coupling is not automatically required in every sequence, but incomplete incorporation should be considered when crude LC-MS shows the corresponding deletion product. Because the α-carbon has no α-hydrogen, the usual α-proton deprotonation pathway for coupling-induced epimerization is not the primary concern; steric accessibility and coupling completion are generally more relevant practical variables.

Applications in Peptide Design

Fmoc-α-Me-Lys(Boc)-OH can be used in linear, cyclic and modified peptide programs when a lysine-derived residue with increased backbone substitution is desired. Typical applications include conformational scans, noncanonical amino-acid libraries, receptor- or protein-binding peptide SAR, proteolytic-stability studies and synthesis of medicinal-chemistry peptide analogs.

The residue should not be assumed to improve affinity or stability in every peptide. Its value comes from creating a defined structural perturbation that can be compared experimentally with the corresponding L-lysine analog.

Procurement and QC Considerations

Confirm CAS 1202003-49-3, molecular formula C27H34N2O6, molecular weight 482.57 g/mol and the (S)-configured α-methyllysine structure on the lot-specific COA. We also recommend checking analytical identity carefully when α-methyl and Nε-methyl lysine building blocks are used in the same program because they can share the same formula and nominal mass.

For storage, keep the material tightly closed under the conditions stated on the product label or lot-specific COA. Supplier documentation for this building block commonly specifies refrigerated storage at 2-8°C.

Product Documents

A Safety Data Sheet (SDS / MSDS) is available for this product to support laboratory handling, storage and safety assessment.

MSDS_Fmoc-alpha-Me-Lys-Boc-OH_AS2144

Certificates of Analysis (COAs) are batch-specific. Please contact us to request the COA for your product, and we will provide it by email.

Frequently Asked Questions

What is Fmoc-α-Me-Lys(Boc)-OH used for?

It is used to introduce α-methyllysine into peptides for conformationally constrained peptide design, noncanonical amino-acid SAR and related peptide-synthesis research.

Is Fmoc-α-Me-Lys(Boc)-OH the same as Fmoc-Lys(Me,Boc)-OH?

No. Fmoc-α-Me-Lys(Boc)-OH carries the methyl group on the α-carbon, whereas Fmoc-Lys(Me,Boc)-OH represents a side-chain methylated lysine derivative. Their identical nominal molecular mass can make structure-level identity checks especially important.

Does α-methyllysine require special coupling conditions?

Not always, but α-methyl substitution increases steric demand. Difficult sequences may benefit from optimized activation, higher equivalents, repeated coupling or direct monitoring of coupling completion.

What happens to the Boc group during final cleavage?

Under a standard Fmoc/tBu strategy, the ε-Boc group is normally removed during final acid-mediated cleavage and global side-chain deprotection, regenerating the lysine side-chain amino group.

Related Technical Resources

Compare this noncanonical residue with the standard lysine building block Fmoc-Lys(Boc)-OH for routine Fmoc-SPPS.

For broader design context, review how noncanonical amino acids expand peptide chemical space.

Browse additional specialty peptide building blocks for α-methyl residues, protected fragments and other nonstandard amino acids.

For complete sequence development, Alan Scientific also supports custom peptide synthesis with noncanonical residues.

Research Use Only.