Scholarlink

<p>Collagen’s structural integrity and biological function derive from its characteristic triple helix, governed by a unique amino acid sequence containing the rare residue (2S,4R)-hydroxyproline (4R-Hyp). Substituting 4R-Hyp with its diastereomer 4S-Hyp markedly reduces triple-helix thermal stability and impairs collagen function. The origins of this destabilization have mostly been ascribed to stereoelectronic effects such as the gauche effect and n&#xa0;→&#xa0;<i>π</i>* interactions. Here, we dissect the role of different stabilizing interactions on molecular conformation using linear infrared and two-dimensional infrared spectroscopy, aided by density functional theory calculations. We investigate the structure of <i>N</i>-Boc-(2S,4S)-4-hydroxyproline-methyl ester (Boc-4S-Hyp-OMe) and <i>N</i>-Boc-(2S,4R)-4-hydroxyproline-methyl ester (Boc-4R-Hyp-OMe) in chloroform solution, a simplified model for the water-deficient environment in collagen tissues where triple helices assemble into fibrils. We find that, while stereoelectronic effects indeed influence molecular conformation, n&#xa0;→&#xa0;<i>π</i>* interactions only moderately alter conformational equilibria. Conversely, our results show that hydrogen bonding is pivotal: the conformation of Boc-4S-Hyp-OMe is stabilized by an intramolecular hydrogen bond, whereas Boc-4R-Hyp-OMe primarily forms intermolecular hydrogen bonds, leading to a greater intermolecular affinity. These findings highlight hydrogen bonding as a key determinant of hydroxyproline conformation at the single-residue level.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Stereoelectronic and hydrogen-bonding effects on hydroxyproline conformation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月24日

查看全文
  • Fumiki Matsumura,
  • Pablo Gómez Argudo,
  • Mischa Bonn,
  • Giulia Giubertoni,
  • Johannes Hunger

摘要

Collagen’s structural integrity and biological function derive from its characteristic triple helix, governed by a unique amino acid sequence containing the rare residue (2S,4R)-hydroxyproline (4R-Hyp). Substituting 4R-Hyp with its diastereomer 4S-Hyp markedly reduces triple-helix thermal stability and impairs collagen function. The origins of this destabilization have mostly been ascribed to stereoelectronic effects such as the gauche effect and n → π* interactions. Here, we dissect the role of different stabilizing interactions on molecular conformation using linear infrared and two-dimensional infrared spectroscopy, aided by density functional theory calculations. We investigate the structure of N-Boc-(2S,4S)-4-hydroxyproline-methyl ester (Boc-4S-Hyp-OMe) and N-Boc-(2S,4R)-4-hydroxyproline-methyl ester (Boc-4R-Hyp-OMe) in chloroform solution, a simplified model for the water-deficient environment in collagen tissues where triple helices assemble into fibrils. We find that, while stereoelectronic effects indeed influence molecular conformation, n → π* interactions only moderately alter conformational equilibria. Conversely, our results show that hydrogen bonding is pivotal: the conformation of Boc-4S-Hyp-OMe is stabilized by an intramolecular hydrogen bond, whereas Boc-4R-Hyp-OMe primarily forms intermolecular hydrogen bonds, leading to a greater intermolecular affinity. These findings highlight hydrogen bonding as a key determinant of hydroxyproline conformation at the single-residue level.