CAJ | 학술논문

硫酸乙酰肝素（HS）通过与蛋白质的相互作用参与了所涉及到的许多动物生物学功能的调控过程，并在其中发挥了重要作用。作为HS特殊结构形式的肝素（HP）也在临床上被广泛用作抗凝药物，并在抗癌、抗炎方面显示出极有希望的药用前景。天然的HS/HP是在糖链长度和磺基化模式等方面具有显著差异的混合物，限制了其结构与功能的进一步阐明和药用价值的进一步开发利用。作为化学合成的替代途径新发展起来的化学酶学合成近期取得了明显突破，缩短了合成过程，显著提高了得率，并加快了HS/HP结构与功能关系的阐明，获得了具有新结构、药用价值更高、抗凝活性可逆的低相对分子质量肝素（LMWH）。随着化学酶学合成技术的逐步改进和对结构与功能的进一步深入了解，合成结构专一、药效更好更稳定、副作用更小的HS/HP药物在今后将逐步实现。文章针对HS/HP化学酶学合成方面的研究进展进行了综述。
류산을선간소（HS）통과여단백질적상호작용삼여료소섭급도적허다동물생물학공능적조공과정，병재기중발휘료중요작용。작위HS특수결구형식적간소（HP）야재림상상피엄범용작항응약물，병재항암、항염방면현시출겁유희망적약용전경。천연적HS/HP시재당련장도화광기화모식등방면구유현저차이적혼합물，한제료기결구여공능적진일보천명화약용개치적진일보개발이용。작위화학합성적체대도경신발전기래적화학매학합성근기취득료명현돌파，축단료합성과정，현저제고료득솔，병가쾌료HS/HP결구여공능관계적천명，획득료구유신결구、약용개치경고、항응활성가역적저상대분자질량간소（LMWH）。수착화학매학합성기술적축보개진화대결구여공능적진일보심입료해，합성결구전일、약효경호경은정、부작용경소적HS/HP약물재금후장축보실현。문장침대HS/HP화학매학합성방면적연구진전진행료종술。
Heparan sulfate (HS)takes part in regulation of many related animal biological functions by its interaction with proteins and plays an important role. As a special structure type of HS,heparin (HP)is also widely used as clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Natural HS and HP are highly heterogeneous mixtures differing in their polysaccharide chain lengths,sulfation patterns and so on,which restricts elucidation of the relationship between their structures and functions and further application of their drug potential. There has recently been a breakthrough in chemoenzymatic method developed for an alternative approach different from chemical synthesis,which shortens the synthesis and improves the product yields significantly. Application of chemoenzymatic synthesis accelerates elucidation of structure-function relationships in HS/HP and low-molecular-weight heparins (LMWH) with reversible anticoagulative activity have been obtained. Along with improvement and optimization of chemoenzymatic method and further understanding of structure-function relationship,it will gradually become possible to synthesize structure-specific HS/HP drugs with better and more stable effects and less adverse effects in the future. Recent progress of HS/HP chemoenzymatic synthesis is summarized in this review.