Some advances in chemistry come from careful patience more than game-changing discoveries. You can trace the road to (4S)-4-Cyclohexyl-L-Proline back to early work on amino acids in peptide engineering. Once researchers started to adjust Proline’s structure by swapping its cyclic ring for something bulkier, such as a cyclohexyl group, things opened up for custom peptide synthesis. This progress didn’t spring from nowhere. Before 1980, organic chemists were working to coax higher selectivity and rigidity out of designer amino acids for better pharmaceutical leads. Efforts in the late 20th century nailed down efficient routes to these non-natural amino acids, laying the groundwork for products that go beyond the usual L-Proline. By the early 2000s, demand grew for tools that let chemists fine-tune protein conformations and block unwanted side reactions, especially in drug design. (4S)-4-Cyclohexyl-L-Proline walked onto the stage for these roles, hand in hand with improvements in asymmetric synthesis.
You can pick up (4S)-4-Cyclohexyl-L-Proline as a solid white or off-white powder, usually pure enough for biochemistry work. Built off the classic L-Proline core, this version swaps the hydrogen at the fourth carbon for a cyclohexyl group, adding both girth and hydrophobicity. A chemist friends the rigid, puckered ring; an engineer notes the boost in solubility profiles. Folks working in peptide synthesis value this compound for what it delivers — stubborn resistance to unwanted backbone flexibility, which lets you build peptides with just the right kinks. Researchers have logged solid performance both in academic settings and industrial builds, finding a fit for this molecule wherever classic amino acids fall short.
(4S)-4-Cyclohexyl-L-Proline lands with a molecular formula of C12H21NO2, massing in at a neat 211.30 g/mol. Pure samples come as crystalline powders, stable under ambient air for months if kept dry. The compound resists high heat, holding shape until above 200°C (melting point varies slightly depending on hydration). Water solubility sits at moderate levels, but organic solvents — methanol, ethanol, DMF — chew it up quickly, making it workable for peptide couplings. The cyclohexyl ring at position 4 imparts higher lipophilicity versus standard Proline, showing up in altered chromatographic retention times and improved compatibility with hydrophobic environments. This altered side chain also reshapes the pKa values for both the amino and carboxyl groups, something to remember when designing experiments or scale-up processes.
Lab supply firms ship this amino acid with tight purity specs — 98% or better, measured by HPLC. Labels call out stereochemistry (4S), usually referencing its optical rotation for confirmation. CAS number 124059-19-0 appears on every drum and vial. Companies follow GHS guidance, printing hazard codes and recommended PPE. Bulk packaging comes in nitrogen-purged bottles to avoid moisture uptake, and each lot carries certificates for heavy metals, enantiomeric excess, and trace residues. That’s become standard, with pharmaceutical buyers pushing for full transparency as part of GMP supply chains. Batch traceability draws on both production logs and chromatographic fingerprints, letting users backtrack if troubles show up downstream.
The world of synthetic amino acid production keeps most details tight, yet the general approach for (4S)-4-Cyclohexyl-L-Proline relies on two maneuvers — chiral pool synthesis and asymmetric catalysis. One common starting point uses L-Proline itself or a protected L-hydroxyproline. Chemists run alkylation reactions with cyclohexyl derivatives under base and phase-transfer conditions, guided by protecting groups to steer the cyclohexyl group onto the right carbon, all set by the (S) configuration. Another well-used play calls for chiral auxiliary-directed alkylation, then removal of the auxiliary to restore free amino acid. Purification leans on repeated extraction and crystallization cycles, with fine-tuning at the end by flash chromatography. Quality control screens for regioisomeric and enantiomeric impurities; high-end users add mass spectrometry checks.
Once you’ve got this molecule in hand, it plays well in standard peptide coupling reactions, joining other amino acids using EDC, HATU, or DCC protocols. Both acid and amine functionalities remain open for typical protection and deprotection strategies. This variant shows less reactivity toward epimerization than native Proline under strong coupling conditions, making it easier to hold onto stereochemical integrity through multiple reaction steps. Side-chain manipulation stays limited by the cyclohexyl’s stubborn inertness, but selective hydrogenation or bromination offers some routes to diversifying the core. Researchers push further using fluorination at the cyclohexyl ring, looking for improved metabolic stability or altered binding in protein matrices. The compound withstands moderate acid and base strengths, so standard SPPS (solid phase peptide synthesis) protocols run smoothly.
Depending on the supplier or catalog, (4S)-4-Cyclohexyl-L-Proline carries different handles: 4-Cyclohexylproline, 4-CHP, or even Cx-Pro for short. Some academic papers use ‘L-4-cyclohexylproline’ or ‘(S)-4-cyclohexylproline’ to mark stereochemistry. You’ll also find the chemical name as (2S,4S)-4-Cyclohexylpyrrolidine-2-carboxylic acid in more technical databases. Each name pays tribute to the backbone (Pyrrolidine ring) with a nod to proline’s placement in peptide chains.
Working with amino acids like this one calls for respect, though you won’t face the hazards linked to many industrial chemicals. Glove use, eye protection, and lab coats form the norm against mild irritancy. Safety data sheets say the compound may irritate skin, eyes, or mucus membranes if you go splashing it around. Accidental inhalation seems rare given its low vapor pressure, but any solid dust can be trouble in an open flask — ventilation helps. Disposal routes mirror those for amino acids in general, running through non-hazardous waste with documentation. Spill controls and cleanup follow standard operating procedures for organic solids with water solubility. Storage out of direct sunlight, dry and cool, prevents hydrolysis or slow oxidative side reactions, preserving shelf life.
Peptide synthesis shops lean hard on (4S)-4-Cyclohexyl-L-Proline for making constrained peptides that resist enzymatic chop-down inside living bodies. Pharmaceutical R&D teams use these building blocks to block kinks and control protein folding in drug candidates — especially those that go after protein–protein interaction sites in diseases like cancer and autoimmune conditions. Medicinal chemists see value in improved serum half-life and lower off-target degradation. Outside pharma, researchers also test this amino acid in designer enzyme catalysts, where its hydrophobic side chain shapes the microenvironment around the active site. Studies keep branching into creating biosensors and smart materials that need sturdy peptide backbones to withstand industrial processing.
Research on (4S)-4-Cyclohexyl-L-Proline has explored many angles: structure–activity relationships in peptides, ribosomal incorporation in synthetic biology, and tuning the compound’s electronic effects through fluorination or aryl substitution. In big pharma, programs run screens on libraries of modified peptides to pick out promising hits for resistant infections or novel pain pathways. Academic groups tweak the side chain to understand its effects on helical propensity and β-turn formation. Publications map out its influence on target selectivity and probe its resistance to enzymatic hydrolysis. Research consortia try to link up these findings so improved amino acids can transition from benchtop demonstration into practical drug design and advanced materials.
Safety studies on (4S)-4-Cyclohexyl-L-Proline lie mostly in cell and animal models, building a picture of its tolerability. Compared to classic L-Proline, the modified side chain brings no obvious spikes in acute or chronic toxicity under standard exposure levels. Rodent dosing tracks clearance pathways and looks for bioaccumulation, while enzyme panels check its structural impact on metabolic breakdown. Most toxicity work so far points to no mutagenic or carcinogenic risk, but deeper studies keep ongoing, especially with increased use in clinical pipelines. Any new amino acid that enters fine chemical supply needs a full toxicology book to avoid late-stage regulatory snags.
There’s a strong trend toward looking beyond natural amino acids for new therapeutic strategies, as resistance and drug stability head the list of industry headaches. (4S)-4-Cyclohexyl-L-Proline forms part of this new toolkit. Its ability to enforce structure in peptides, combined with manageable synthesis and safety, creates chances both in targeted medicines and in advanced material science. Synthetic biologists see potential for in vivo incorporation into cellular factories, opening entirely new spaces for enzyme performance and pathway engineering. The field watches for breakthroughs around scalable, green chemistry production and next-gen analogues with improved pharmacokinetics. In the lab and in industry, molecules like this nudge biochemistry forward, building more durable, specific, and smart applications year by year.
