trans-3-Hydroxy-L-proline (CAS 4298-08-2, (2S,3S)-3-hydroxypyrrolidine-2-carboxylic acid) is a chiral, non-proteinogenic amino acid used as a building block in macrocyclic peptide synthesis. Hzymes supplies it with NMR and HPLC-ELSD reports and solubility data.

trans-3-Hydroxy-L-proline is a proline derivative with the hydroxyl group on carbon 3 of the pyrrolidine ring, trans to the carboxyl group. It is not trans-4-hydroxy-L-proline (CAS 51-35-4), the common hydroxyproline of collagen, so confirm the CAS number before ordering. As a conformationally constrained chiral synthon, it is used to build macrocyclic peptides and their intermediates. Hzymes lists it in its Enlicitide (MK-0616) building-block series with purity of 99.9% by HPLC, dual NMR/HPLC-ELSD detection reports, and solubility data in DMSO and PBS.

Product Overview

trans-3-Hydroxy-L-proline (Hzymes catalog name: Trans-3-Hydroxy-L-proline) is a hydroxylated analogue of L-proline. The ring constraint of proline, combined with a defined C3 hydroxyl group and fixed (2S,3S) stereochemistry, makes it a useful chiral synthon for macrocycles and conformationally restricted peptides.

Because the molecule has no strong UV chromophore, Hzymes supports purity assessment with two complementary methods, NMR and HPLC with evaporative light scattering detection (HPLC-ELSD), and provides solubility data in DMSO and PBS to help with reaction and formulation planning.

Hydroxyproline isomers are easy to confuse. Verify the CAS number and stereodescriptors on the COA.

Key Features

High Optical Purity

With ee ≥ 99.0%, trans-3-hydroxy-L-proline supports stereochemically controlled synthesis and helps minimize the impact of unwanted stereoisomeric impurities in downstream applications.

Rigid Conformational Structure

The trans-3-hydroxy substitution can influence the conformational preferences of peptide backbones. This makes the compound useful for studying peptide conformational control and structure–activity relationships.

Additional Hydroxyl Functionality

Compared with conventional proline, trans-3-hydroxy-L-proline contains an additional hydroxyl group that can serve as a versatile chemical handle for protection, functionalization, and structural optimization.

Versatile Synthetic Building Block

The secondary amine and hydroxyl group provide opportunities for selective modification, making trans-3-hydroxy-L-proline suitable as a t3Hyp peptide building block in peptide and medicinal chemistry workflows.

Research Applications in Hydroxyproline Biochemistry

Hydroxyproline derivatives are widely studied in collagen biology and enzyme-mediated amino acid modification. Trans-3-hydroxy-L-proline can therefore serve as a useful research compound for investigating proline hydroxylation enzyme substrates and related biochemical pathways.

Applications

Peptide Drug Development

Trans-3-hydroxy-L-proline can be incorporated into peptide-oriented research as a proline analogue to investigate changes in peptide conformation, metabolic stability, and target binding.

Its structural properties make it particularly relevant to researchers evaluating hydroxyproline-containing sequences and specialized t3Hyp peptide building blocks.

Collagen and Protein Structure Research

Hydroxyproline plays an important structural role in collagen. Research involving hydroxyproline can contribute to understanding collagen triple helix stabilization, protein folding, and collagen-related enzymatic processes.

Trans-3-hydroxy-L-proline can be used as a research building block or analytical reference in studies related to hydroxyproline and collagen synthesis.

Prolyl Hydroxylase Research

The compound is relevant to biochemical studies investigating proline hydroxylation and the substrate specificity of prolyl hydroxylase enzymes. Such research can help characterize enzyme activity, substrate recognition, and hydroxylation mechanisms.

Pharmaceutical and Chiral Synthesis

With its defined stereochemistry and functionalized pyrrolidine structure, trans-3-hydroxy-L-proline can serve as a chiral building block for pharmaceutical research, particularly for the synthesis and optimization of bioactive molecules.

Natural Product and Peptide Biosynthesis Research

Hydroxyproline-containing structures occur in various natural products and non-ribosomal peptides. Hydroxyproline-related building blocks may therefore be relevant to research on non-ribosomal peptide antibiotic precursors and specialized peptide biosynthetic pathways, including studies of echinocandin biosynthesis and hydroxyproline.

Enzyme and Biochemical Research

The compound can be used as a substrate, analogue, or structural probe in studies involving amino acid hydroxylation, enzyme specificity, and hydroxyproline metabolism. It may also support research related to enzyme-based or recombinant hydroxyproline production strategies.

Published literature describes two broad approaches to 3-hydroxyproline: biocatalytic hydroxylation of proline using proline hydroxylase enzymes, and multi-step chemical synthesis from chiral-pool precursors such as L-glutamic acid, including cyclization strategies. This overview reflects public literature only and does not describe Hzymes' own manufacturing process. For custom synthesis or scale-up inquiries, contact Hzymes with your specification and timeline.

•     Cbz-trans-3-hydroxy-L-proline: benzyloxycarbonyl-protected nitrogen, removed by hydrogenolysis.

•     Boc-trans-3-hydroxy-L-proline (CAS 187039-57-2): acid-labile Boc protection.

1.      WO2019246386, Cyclic polypeptides for PCSK9 inhibition (Ra Pharmaceuticals, 2019).

2.      Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases. PMC3252868.

References are listed for background only; they do not imply that any listed document covers this product or Hzymes' process.

FAQ

Q1: What is trans-3-hydroxy-L-proline?

A: Trans-3-hydroxy-L-proline is a non-natural hydroxyproline derivative with a rigid pyrrolidine ring and a hydroxyl group at the 3-position. It is used as a specialized building block in peptide synthesis, medicinal chemistry, and biochemical research.

Q2: What is the CAS number of trans-3-hydroxy-L-proline?

A: The CAS number is 4298-08-2. Researchers searching for trans-3-hydroxy-L-proline CAS 4298-08-2 can use this identifier for product and literature searches.

Q3: What is the difference between trans-3- and trans-4-hydroxy-L-proline?

A: They differ in where the hydroxyl group sits on the proline ring: carbon 3 versus carbon 4. trans-4-Hydroxy-L-proline is the main hydroxyproline of collagen. They are different compounds with different CAS numbers and are not interchangeable in synthesis.

Q4: Can trans-3-hydroxy-L-proline be used as a peptide building block?

A: Yes. Its defined stereochemistry, rigid cyclic structure, and additional hydroxyl group make it useful as a specialized peptide building block for investigating peptide conformation and biological activity.

Q5: Is trans-3-hydroxy-L-proline related to collagen research?

A: Yes. Hydroxyproline is an important amino acid derivative in collagen biology. Hydroxyproline-related research is commonly associated with collagen structure, collagen triple helix stabilization, and collagen biosynthesis. Trans-3-hydroxy-L-proline can serve as a useful research compound for studying these areas.

Q6: Can it be used in prolyl hydroxylase studies?

A: It can be considered for biochemical research involving proline hydroxylation and prolyl hydroxylase substrate specificity. Suitability should be evaluated according to the specific enzyme, assay system, and experimental objective.

Q7: Can it be used directly in solid-phase peptide synthesis?

A: For peptide synthesis the ring nitrogen normally needs protection first, and depending on the coupling strategy the 3-hydroxyl group may also need protection. Hzymes offers the Cbz- and Boc-protected derivatives; see the links on this page.

Q8: Does the hydroxyl group need to be protected?

A: Protection depends on the synthetic route. When subsequent reactions involve strongly basic conditions or acylation chemistry, hydroxyl protection may be appropriate. Common strategies include TBS or acetyl (Ac) protection.

Q9: What are the recommended storage conditions?

A: Store at 2–8°C in a dry, light-protected environment. The material should be tightly sealed after use to minimize exposure to moisture.

Q10: What should I consider when selecting a trans-3-hydroxyproline supplier?

A: Key factors include optical purity, chemical purity, batch-to-batch consistency, analytical documentation, packaging, and technical support. Hzymes Biotech supplies high-purity amino acid building blocks for pharmaceutical, peptide, and biochemical research applications.

Q11: What documentation does Hzymes provide?

Hzymes provides NMR and HPLC-ELSD detection reports and solubility data in DMSO and PBS. Request the COA and reports with your quote.