trans3hydroxyproline

Trans-3-hydroxyproline is a non-proteinogenic amino acid, a hydroxylated derivative of proline in which a hydroxy group is located at the C-3 position of the pyrrolidine ring. The designation “trans” refers to the stereochemical relationship of substituents on the ring and helps distinguish this isomer from other hydroxyproline forms. It is biosynthetically related to prolyl hydroxylation but is far less abundant than the well-known trans-4-hydroxyproline found in collagen.

Occurrence and biosynthesis: Trans-3-hydroxyproline has been identified in collagen and collagen-like proteins in some organisms, produced by prolyl-3-hydroxylase enzymes in a tissue- and species-specific manner. In mammals, 3-hydroxylation is relatively rare compared with 4-hydroxylation and can contribute to local structural variation within the triple helix of collagen or in related matrices.

Chemistry and synthesis: Trans-3-hydroxyproline can be prepared synthetically and is available in enantiopure forms for research use. For peptide synthesis, protected derivatives suitable for solid-phase synthesis (for example, Fmoc- or Boc-protected trans-3-hydroxyproline) are used to incorporate the residue at specific positions. In peptides and collagen-mimetic systems, the 3-hydroxy modification can influence conformational preferences and hydrogen-bonding networks.

Analytical properties and applications: Detection and characterization typically involve chromatographic separation after acid hydrolysis or direct mass spectrometry of intact proteins, complemented by NMR to confirm ring stereochemistry. Functionally, 3-hydroxyproline residues are studied as probes of how hydroxy modifications affect collagen stability, folding, and intermolecular interactions. Trans-3-hydroxyproline thus serves as a tool in structural biology and biomaterials research.

See also: hydroxyproline, proline, prolyl hydroxylases, collagen.