Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Biological Roles of the Glycan in the Investigation of the Novel Disease Diagnosis and Treatment Methods

신개념 질병 진단 및 치료 연구에 있어서의 당사슬의 생물학적 역할

  • Kim, Dong-Chan (Department of Biomedical Laboratory Science, Gimcheon University)
  • 김동찬 (김천대학교 임상병리학과)
  • Received : 2018.11.01
  • Accepted : 2018.11.21
  • Published : 2018.11.30
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Abstract

Glycans are attached to proteins as in glycoproteins and proteoglycans. They are found on the exterior surface of cells. O- and N-linked glycans are very common in eukaryotic cells but may also be found in prokaryotes. The interaction of cell surface glycans with complementary glycan binding proteins located on neighboring cells, other cell types, pathogens like virus, or bacteria is crucial in biologically and biomedically important processes like pathogen recognition, cell migration, cell-cell adhesion, development, and infection. Their implication in pathological condition, suggests an important role for glycans as disease markers. In addition, a great amount of research has been shown that appropriate glycosylation of a recombinant therapeutic protein is critical for product solubility, stability, pharmacokinetics and pharmacodynamics, bioactivity, and safety. Besides, cancer-associated glycosylation changes often involve sialic acid in glycan branch which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the glycan's biological function and describing the relevance among the glycosylation, disease diagnosis and treatment methods. Furthermore, the high-throughput analytic methods available to measure the profile changing patterns of glycan in the blood serum as well as possible underlying biochemical mechanisms.

당사슬은 당단백질과 단백당에 결합하며, 일반적으로 세포의 최외각 표면에서 발견된다. O-연결 당사슬과 N-연결 당사슬은 진핵세포에 흔히 존재하는 당사슬이며 원핵세포에서도 발견된다. 세포 표면에 존재하는 당사슬과 주변에 동일한 종류의 세포막에 노출된 당사슬 결합 단백질과의 상호작용, 전혀 다른 종류의 세포와의 상호작용, 또는 질병 유발 균주와 바이러스와의 상호작용은 생물학 및 의생명과학에 있어서 질병원인물질 인식, 세포 이동, 세포간의 결합, 발생, 그리고 감염 등과 같은 과정에 있어서 매우 중요한 역할을 담당한다. 각종 질병 상황에서의 당사슬의 프로파일의 변화와 역할은 당사슬이 질병 진단 마커로 활용할 가능성을 제시한다. 이에 더하여, 기존의 많은 선행 연구들에서, 재조합 단백질 의약품에 결합된 당사슬은 재조합 단백질 의약품의 용해도, 약동역학, 약물 활성, 생체활성, 안전성을 적절하게 유지하고 결정짓는데 중요한 요소가 된다. 게다가, 암의 발생과 진전의 영향으로 인해 당사슬 가지 끝에 결합하는 시알릭산의 당질화 양상의 변화는 세포와 세포간 상호작용, 인식 그리고 면역 반응에 매우 중요한 요소로 작용한다. 본 총설에서는 당사슬의 생물학적인 기능에 대한 전반적인 이해를 돕고, 당질화 현상과 질병 진단 및 질병 치료 기법간의 상호 연관성을 간략히 설명하고자 한다. 추가적으로 혈액 내 혈청에 존재하는 당사슬의 프로파일의 변화를 분석하는 대량효능검색 방법과 이로 인해 유도되는 생화학적 작용 기작을 살펴보았다.

Keywords

SMGHBM_2018_v28n11_1379_f0001.png 이미지

Fig. 1. Schematic representation of N-linked and O-linked glycans on glycoproteins and glycolipids [44].

SMGHBM_2018_v28n11_1379_f0002.png 이미지

Fig. 2. Accelerating progress in the discovery of human glycosylation disorders. The graph shows the cumulative number of human disorders with a major genetic defect in various glycosylation pathways and the year of their identification. In early years, initial discovery was based on compelling biochemical evidence, and in later years by conclusive genetic proof. In most instances, the year indicates the occurrence of definitive proof of gene-specific mutations and correlations to biochemical results [38].

SMGHBM_2018_v28n11_1379_f0003.png 이미지

Fig. 3. Schematic diagram of the plasma membrane (left). The spheres are saccharides attached to proteins (glycoprotein). The arrows indicate the sialic acids attached to terminal positions of glycoproteins. The structure of sialic acid (α2-3) galactose is presented on the right [41].

SMGHBM_2018_v28n11_1379_f0004.png 이미지

Fig. 4. N-glycan MALDI mass spectrometry imaging (MSI) of stage I (n=3) and stage III (n=3) serous ovarian cancer patients. Formalin-fixed paraffin-embedded tissue sections were treated with citric acid antigen retrieval prior to printing of dialyzed PNGase F with 250 μm spacing. DHB matrix was sprayed onto the sections and MS spectra were acquired by oversampling at 100 μm intervals using a MALDI-TOF/TOF MS instrument. Monoisotopic glycan masses were measured in the positive ion reflectron mode as (M + Na) adducts for MALDI-MSI whereas PGCLC-ESI-MS/MS revealed doubly negatively charged monoisotopic masses ([M-2H] 2-). Panels A-F show ion intensity maps of m/z 16663.581 from the stage I (green) and stage III (red) patients. The N-glycan, (Hex)1 (HexNAc)3 (Deoxyhexose) 1 + (Man)3(GlcNAc)2, in panel G is the confirmed structure based on PGC chromatography (panel H) and MS/MS fragmentation (panel I) [4].

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