N‑methylation, β/γ amino acids, peptoids, and peptide‑bond isosteres—engineered for stability, conformation, and permeability.
In peptide chemistry, a backbone modification changes the peptide framework—such as the amide nitrogen (N‑methylation), α‑carbon stereochemistry (D‑amino acids), backbone length (β/γ amino acids), or the amide bond itself (e.g., ψ[CH2NH] reduced amide). These changes can reduce hydrogen‑bond donors, restrict conformational space, alter folding, and improve resistance to proteolysis—key levers for peptidomimetics, cyclic peptides, and permeability optimization.
Bio‑Synthesis provides custom synthesis of backbone‑modified peptides and peptidomimetics with project‑aligned purification and QC (HPLC/UPLC and LC‑MS when feasible). We support major backbone modification classes used in modern peptide and foldamer design—including N‑methylated peptides, β/γ amino acid peptides (foldamers), and peptoids (N‑substituted glycines).
Backbone modification types showing N-methylation, peptoids, α-methyl residues, D-amino acids, β/γ amino acids, and reduced amide bonds.
Related pages: Peptidomimetics, Macrocyclic peptides, Peptide cyclization, Difficult peptide synthesis .
For fastest scoping, send your sequence, intended use (assay vs drug discovery), and your failure mode (proteolysis, permeability, aggregation). We’ll propose a ranked modification plan and QC.
There is no finite “complete” list of backbone‑modified amino acids across all chemistry—new building blocks and protected derivatives are continually developed. Below are the major, widely used categories that cover most backbone‑modified peptide and peptidomimetic designs.
If you have a specific protected monomer (Fmoc/Boc derivative) in mind, send the catalog name or structure and we’ll confirm feasibility and route.
N‑methylation adds a methyl group to the amide nitrogen, reducing backbone H‑bond donors and restricting conformational space—commonly used to improve stability and permeability in cyclic peptides and peptidomimetics (sequence‑dependent).
Practical note: multiple N‑methyl residues may require double coupling and route optimization.
β‑amino acids add an extra backbone carbon relative to α‑amino acids. β‑peptides and α/β‑peptides can form stable foldamer architectures and are widely used to increase protease resistance and control conformation.
Practical note: coupling and purification may require adjustment due to altered spacing/hydrophobicity.
Peptoids place side chains on the amide nitrogen rather than the α‑carbon, typically improving resistance to enzymatic/protease degradation and enabling broad peptidomimetic design space.
Reduced amide (ψ[CH2NH]) and related isosteres can create non‑hydrolyzable bonds for stability enhancement or enzyme mechanism studies. Feasibility depends on the target position and sequence context.
D‑substitutions invert backbone stereochemistry and can dramatically increase protease resistance. They’re also used as matched controls (L vs D) to validate binding specificity.
Connect backbone modification with constrained scaffolds, labeling, and challenging sequences.
Remove or adjust any link paths you’re not using yet—this block is designed to be modular.
If your decision depends on stability, binding, permeability, or labeling efficiency, tell us and we’ll align QC to it.
A peptide containing building blocks that alter the backbone itself (amide N, stereochemistry, spacing, or the bond), which can change hydrogen bonding, folding, stability, and permeability versus standard α‑peptides.
N‑methylation reduces backbone H‑bond donors and can restrict conformational space—often used to increase stability and permeability in cyclic peptides and peptidomimetics (sequence‑dependent).
Often yes—β‑peptides and α/β‑peptides are used as foldamers and can resist proteolysis compared with native peptides, while adopting stable secondary structures.
Yes. Peptoids are commonly synthesized by solid‑phase methods and are valued for protease resistance and peptidomimetic design space.
Yes—reduced amide bonds and related isosteres can be used as non‑cleavable surrogates for stability or enzyme mechanism studies. Feasibility depends on position and sequence context.
Send your sequence, the exact monomer(s) and position(s) (or “recommend”), your intended use (assay vs drug discovery), quantity/purity targets, and any constraints on preserving a motif.
For the fastest quote, send your sequence(s), backbone modification(s) + positions (or “recommend”), desired quantity/purity, and intended use. We’ll propose a practical synthesis route and QC plan aligned to your goals.
Peer-reviewed background on backbone modification strategies used in peptides and peptidomimetics.
Want a reading list tuned to your modification (N-Me vs β-AA vs peptoid vs ψ[CH2NH]) and target class? Tell us your application and we’ll tailor it.
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