3-(4-Pyridyl)-D-alanine: Properties, Uses & Research Guide
3-(4-Pyridyl)-D-alanine: Properties, Uses & Research Guide
3-(4-Pyridyl)-D-alanine is a non-canonical, enantiopure D-configured amino acid bearing a 4-pyridylmethyl side chain, widely employed as a versatile building block in peptide chemistry, peptidomimetic design, and medicinal chemistry research.
- Chemical Name
- 3-(4-Pyridyl)-D-alanine
- Molecular Formula
- C₈H₁₀N₂O₂
- Molecular Weight
- 166.18 g/mol
- Stereochemistry
- D-configuration (R) at the α-carbon
- Key Functional Groups
- α-amino group, α-carboxylic acid, pyridine ring (4-position)
- SKU
- A107875
- Typical Application
- Peptide synthesis, peptidomimetics, coordination chemistry, drug discovery
Chemical Structure and Physicochemical Properties
3-(4-Pyridyl)-D-alanine belongs to the family of pyridylalanine non-canonical amino acids. Its backbone retains the standard α-amino acid scaffold—an α-amino group and an α-carboxylic acid—while the side chain replaces the typical alkyl or aryl substituent with a 4-pyridylmethyl (4-picolyl) moiety. The compound exists as a zwitterion at physiological pH, analogous to natural amino acids.
The presence of the pyridine nitrogen imparts unique properties: it serves as a hydrogen-bond acceptor, a metal-coordination site, and a weak base (pyridine pKₐ ≈ 5.2), significantly expanding the compound's utility relative to its phenylalanine analogue. The D-configuration at the α-carbon confers resistance to many proteolytic enzymes that selectively cleave L-amino acid residues, making D-configured building blocks attractive for producing metabolically stable peptides.
Key physicochemical parameters (review flags apply—see below):
- Molecular formula: C₈H₁₀N₂O₂
- Molecular weight: 166.18 g/mol
- Appearance: typically a white to off-white crystalline solid
- Solubility: soluble in water and dilute aqueous acid or base; limited solubility in common organic solvents
Synthesis and Availability
3-(4-Pyridyl)-D-alanine can be prepared through several established synthetic strategies used for non-canonical D-amino acids:
- Asymmetric synthesis: Chiral phase-transfer catalysis or use of chiral auxiliaries (e.g., Schiff base glycine equivalents) allows enantioselective alkylation with 4-picolyl electrophiles to install the correct D-stereocenter.
- Resolution of racemates: Chemical or enzymatic resolution of racemic 3-(4-pyridyl)alanine using D-amino acid-selective enzymes or chiral resolving agents can furnish the D-enantiomer in high enantiopurity.
- Chemoenzymatic routes: Transaminases with D-selectivity or D-amino acid dehydrogenases can convert appropriately functionalized keto acid precursors to the target D-amino acid.
For most research laboratories, procurement from a reliable reagent supplier is the most practical approach. Aladdin Scientific supplies 3-(4-Pyridyl)-D-alanine (SKU: A107875) in research-grade quantities, providing a time-efficient alternative to in-house synthesis.
Research Applications
The combination of the D-amino acid backbone and the metal-chelating, hydrogen-bonding pyridine side chain makes 3-(4-Pyridyl)-D-alanine a multifunctional tool across several research domains:
Peptide and Peptidomimetic Chemistry
Incorporation of D-amino acid residues into peptides introduces local conformational constraints and improves proteolytic stability. The 4-pyridyl side chain further enables selective metal coordination, pH-responsive behavior, and additional non-covalent interactions with biological targets. These features are exploited in the design of enzyme inhibitors, receptor ligands, and antimicrobial peptides.
Coordination Chemistry and Metallopeptides
The pyridine nitrogen of the side chain can coordinate to transition metals (e.g., Cu²⁺, Zn²⁺, Pd²⁺), enabling the construction of metallopeptide catalysts, supramolecular assemblies, and bioinorganic model compounds. D-configured residues add stereochemical diversity to such architectures.
Drug Discovery and Medicinal Chemistry
Non-canonical D-amino acids are important pharmacophore elements in peptidomimetic drug design. The pyridine ring can improve aqueous solubility relative to purely carbocyclic aromatic side chains, assist in target engagement through hydrogen bonding, and serve as a bioisostere for certain aromatic heterocycles present in drug candidates.
Biochemical Probes
Labelled or modified derivatives of pyridylalanine residues are used as biochemical probes to study enzyme active-site geometry, substrate specificity, and protein–ligand interactions.
Handling, Storage and Safety Considerations
As with most research-grade amino acid derivatives, standard laboratory safety precautions should be observed when handling 3-(4-Pyridyl)-D-alanine:
- Storage: Store in a cool, dry place away from direct light, in a tightly sealed container. Specific temperature recommendations should be confirmed from the product Certificate of Analysis (CoA).
- Handling: Use appropriate personal protective equipment (PPE) including lab coat, gloves, and eye protection. Avoid generating dust during weighing.
- Solubility tip: For preparation of stock solutions, dissolution in dilute aqueous hydrochloric acid (0.1 M) or dilute aqueous sodium hydroxide is recommended before diluting to the desired buffer system.
- Stability: The compound is generally stable as a dry solid under recommended storage conditions. Prolonged exposure to moisture, heat, or light should be avoided.
Always consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific for comprehensive hazard information before use.
Frequently asked questions
What is the difference between 3-(4-Pyridyl)-D-alanine and its L-enantiomer?
3-(4-Pyridyl)-D-alanine and 3-(4-Pyridyl)-L-alanine are mirror-image enantiomers that share identical molecular formula and weight but differ in the spatial configuration at the α-carbon (R vs S). The D-form is not recognized by most mammalian proteases, resulting in greater metabolic stability of peptides incorporating this residue. In biochemical and pharmacological studies, the two enantiomers can exhibit markedly different biological activities due to the stereoselectivity of their target proteins.
How should I dissolve 3-(4-Pyridyl)-D-alanine for use in peptide synthesis or biological assays?
The compound is most conveniently dissolved in water or dilute aqueous acid (e.g., 0.1 M HCl) to prepare a concentrated stock solution, which can then be diluted into the appropriate reaction buffer. For solid-phase peptide synthesis (SPPS), the protected derivative (e.g., Fmoc- or Boc-protected form) would typically be used and dissolved in DMF or NMP. Always verify solubility in your specific solvent system before large-scale use.
Is 3-(4-Pyridyl)-D-alanine suitable for metal-chelation applications?
Yes. The pyridine nitrogen in the 4-pyridyl side chain is an effective ligand for a range of transition metals, including copper, zinc, and palladium. When incorporated into peptides, it can create multidentate coordination environments together with backbone amide nitrogens or other coordinating residues. This makes the compound valuable for constructing metallopeptides, supramolecular structures, and catalytic scaffolds. The exact coordination geometry and affinity depend on the metal ion and the surrounding peptide sequence.
What purity grade is available for SKU A107875?
Specific purity information for SKU A107875 should be confirmed from the product Certificate of Analysis (CoA) available from Aladdin Scientific. Research-grade amino acid building blocks are typically supplied at ≥98% purity (HPLC), but customers are advised to verify this and any enantiopurity (ee%) data from the CoA prior to use in sensitive applications.
References
- Barrett, G. C.; Elmore, D. T. Amino Acids and Peptides. Cambridge University Press, 1998. (General reference for amino acid chemistry and properties.)
- Genscript / general literature on D-amino acids in peptide medicinal chemistry: Kolbrun Kristmundsdottir et al. Use of D-amino acids in peptide design — review-level textbook knowledge.
- Metzler-Nolte, N. Bioorganometallic Chemistry of Amino Acids, Peptides and Proteins. Angew. Chem. Int. Ed., 2001. (Reference for metal coordination by amino acid side chains including pyridine-containing residues.)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
危险品化学品经营许可证（带存储）