• Title/Summary/Keyword: Glycopeptide

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A Comprehensive Review of Recent Advances in the Enrichment and Mass Spectrometric Analysis of Glycoproteins and Glycopeptides in Complex Biological Matrices

  • Mohamed A. Gab-Allah;Jeongkwon Kim
    • Mass Spectrometry Letters
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    • v.15 no.1
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    • pp.1-25
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    • 2024
  • Protein glycosylation, a highly significant and ubiquitous post-translational modification (PTM) in eukaryotic cells, has attracted considerable research interest due to its pivotal role in a wide array of essential biological processes. Conducting a comprehensive analysis of glycoproteins is imperative for understanding glycoprotein bio-functions and identifying glycosylated biomarkers. However, the complexity and heterogeneity of glycan structures, coupled with the low abundance and poor ionization efficiencies of glycopeptides have all contributed to making the analysis and subsequent identification of glycans and glycopeptides much more challenging than any other biopolymers. Nevertheless, the significant advancements in enrichment techniques, chromatographic separation, and mass spectrometric methodologies represent promising avenues for mitigating these challenges. Numerous substrates and multifunctional materials are being designed for glycopeptide enrichment, proving valuable in glycomics and glycoproteomics. Mass spectrometry (MS) is pivotal for probing protein glycosylation, offering sensitivity and structural insight into glycopeptides and glycans. Additionally, enhanced MS-based glycopeptide characterization employs various separation techniques like liquid chromatography, capillary electrophoresis, and ion mobility. In this review, we highlight recent advances in enrichment methods and MS-based separation techniques for analyzing different types of protein glycosylation. This review also discusses various approaches employed for glycan release that facilitate the investigation of the glycosylation sites of the identified glycoproteins. Furthermore, numerous bioinformatics tools aiding in accurately characterizing glycan and glycopeptides are covered.

Multi-Level Characterization of Protein Glycosylation

  • Hua, Serenus;Oh, Myung Jin;An, Hyun Joo
    • Mass Spectrometry Letters
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    • v.4 no.1
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    • pp.10-17
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    • 2013
  • Recent developments in MS-based glycomics and glycoproteomics have rapidly advanced the field and pushed the boundaries of glyco-analysis into new territories. This review will lay out current workflows and strategies for characterization of the glycoproteome, including (in order of increasing complexity and information content) preliminary site mapping, compositional glycan profiling, isomer-specific glycan profiling, glycosite-specific glycopeptide profiling, and finally, glycoproteomic profiling.

Vaneomycin-Resistant Enteroeocci (VRE) Treatment Options (Vaneomycin-Resistant Enteroeocci (VRE) 약물치료방법)

  • Kim, Myo Kyoung
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.1-14
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    • 1999
  • Vancomycin-resistant Enterococci (VRE) have recently emerged in Korean hospitals, as well as in those of other countries. VRE have been partially attributed to the overuse and misuse of vancomycin. The mecbanisms of VRE resistance are related to VanA, VanB, and VanC. Both VanA and VanB produce abnormal ligase enzymes to form D-ala-D-lactate termini in E. faecium and E. faecalis, instead of D-ala-D-ala termini. Meanwhile, Van C produces D-ser-D-ala termini in E. gallinarum and E. casseliflavus. These abnormal termini have a low affinity to vancomycin. As a result, VRE avoid the activity of vancomycin by these mechanisms. Unfortunately, there is no approved therapy for the treatment of VRE. Thus, available but uncommonly prescribed antibiotics (due to their toxicity or unproven efficacy) may become possible options. They include chloramphenicol, novobiocin, fosfomycin, and bacitracin. The combination therapy of available agents may also be the other options. They include high doses of a penicillin- or ampicillin-aminoglycoside combination, high doses of an ampicillin/sulbactam and aminoglyoosidcs combination, an ampicillin and vancomycin combination, and a ciprofloxacin, aminoglycosides, and rifampin combination. With respect to the near future, many types of investigational agents will most likely expand their treatment options for VRE. Teicoplanin, a glycopeptide, can be used for VanB- and VanC-related VRE. LY333328, a new generation of glycopeptide, is effective in treating VanA as well as VanB and VanC. RP59500 (quinupristin/dalfopristin), a streptogramin, is effective in treating vancomycin-resistant E. faecium. New generation quinolones (especially clinatloxacin) are potential options for the treatment of VRE, even though they cannot work as effectively against VRE as they can against Staphylococci. Both glycylcyclines (a new generation of tetracyclines) and ketolides (a new generation of macrolides) show good activity against Enterococci, regardless of vancomycin susceptibility. Oxazolidinones (i. e. eperezolid and 1inezolid) and everninomicins (i. e. SCH27899) are new groups of antibiotics, which also demonstrate good activity against VRE. It is imperative that clinical pharmacists take the responsibility of investigating new treatment options for VRE in order to combat this growing problem throughout the world.

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그람 양성균 감염증에서 Vancomycin 과 Teicoplanin 의 임상효과의 비교 연구

  • 최강원;오명돈;배현주
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.331-331
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    • 1994
  • 최근 개발된 Teicoplanin은 glycopeptide계의 항생제로서 vancomycin과 그 작용 기전이 비슷하지만, 근육 주사가 가능하고, 반감기가 길어서 하루 한번 주사하여도 되며, 빨리 주입하더라도 red man syndrome이생기지 않는 장점이 있다. 이 연구의 목적은 그람 양성균에 의한 감염증을 치료하는데 teicoplanin이 효과적이고 안전한지를 vancomycin과 비교하는 것이다. 대상 환자 및 방법: 서울대학교병원에 입원하여 그람 양성균 감염증이 확인되거나 강력히 의심되는 환자를 대상으로 하였다. 감염증의 종류는 패혈증, 골수염, 하기도 감염증, 감염성 관절염, 피부 및 연조직 감염증, 요로 감염증으로 하였다. 대상 환자를 무작위로 teicoplanin또는 vancomycin군에 무작위 배정하였다. Teinoplanin은 처음에 loading을 위하여 400mg씩 12시간마다 3회 주사하고 이후에는 증증 감염이면 하루에 400mg, 중등중이면 200mg씩을 주사하였다. Vancomycin은 500mg을 6시간마다 또는 1. 0g을 12시간마다 정맥주사하였다. 치료 기간은 요로 감염증 5-10일, 하기도 감염증 5-10일, 패혈증 14-21일, 골수염 21-42일, 세균성 관절염 21-42일, 피부 및 연조직 감염증 5-10일로 하였다.

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Separation and Purification of Teicoplanin by Diaion HP-20 and Conacnavalin A Chromatography (소수성 Diaion HP-20및 친화성 Concannvalin A 크로마토그래피를 이용한 Glycopeptide계 항생제 Teicoplanin의 분리 및 정제)

  • 김창진;이재찬;박해룡;박동진;김영배
    • Microbiology and Biotechnology Letters
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    • v.31 no.2
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    • pp.201-204
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    • 2003
  • Glycopeptide antibiotics, teicoplanin was purified from a mutant strain of Actinoplanes teichomyceticus ATCC31121, A. teichomyceticus MSL2211. We developed a simple procedure to separate and purify the teicoplanin from the fermentation broth. Teicoplanin was purified by two-step purification system, hydrophobic adsorption and sugar affinity chromatography in combination with HPLC analysis based on the properties of hydrophobic acyl chain and sugar moiety in teicoplanin. Teicoplanin was separated from the culture broth by Diaion HP-20 and further purified by concanavalin A affinity column chromatography. As an adsorbent resin, Diaion HP-20 in broth eliminated toxic effects on growth, reduced feedback repression of teicoplanin production, and assisted In rapid recovery of teicoplanin. The teicoplanin displayed the final yield of 80% and 95% of purity.

그람양성군 감염증에 대한 Teicoplanin과 Vancomycin의 임상 효과 및 그 안전성에 관한 비교 연구

  • 최강원;우준희;오명돈
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1992.05a
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    • pp.57-57
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    • 1992
  • Teicoplanin은 actinoplanes teicomyceticus의 발효산물로서 vancomycin과 같은 glycopeptide 계열의 항균제이며, 그 작용기전은 세포벽 합성과정중 peptidoglycan의 중합을 억제하는 것으로 vancomycin과 유사하나 vancomycin과 달리 근육에 주사할 수 있으며 "red man's syndrome"이 생기지 않고 vancomycin보다 반감기가 길다. 그람양성균 감염증에 대한 teicoplanin의 효능 및 안전성을 조사하기 위하여, 그람양성균에 의한 감염증 또는 그람양성균과 그람음성균에 의한 혼합감염증이 확인되거나 의심되었던 환자 46명을 대상으로 teicoplanin과 vancomycin을 투여하였다. 투약 환자중 임상적인 반응을 평가할 수 있는 환자의 수는 vancomycin의 경우 투약환자 22명중 21명, teicoplanin의 경우 24명중 19명이였다. Vancomycin군중 임상적 반응의 평가에서 제외된 1명은 수술 후 흉막강에 MRSA 에 의한 농양으로 투약 29일째에 뇌출혈로 사망하였던 예로, 추적-배양검사에서는 MRSA가 제거 되었다. Teicoplanin군에서는 항균제 투여 중 간경변증에 의한 식도출혈 1예, 수술후 위장관 출혈 1예, 뇌 색전중 1예가 사망하였고, 1예는 Teicoplanin에 의한 심한 피부발진으로, 다른 1예는 봉와직염의 임상진단이 조직검사결과 악성종양의 근육침범으로 밝혀져 투약을 중단하였다.

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Antitumor and Antioxidant Activities of the Extracts from Fruiting Body of Phellinus linteus

  • Lee, June-Woo;Baek, Seong-Jin;Bae, Woo-Chul;Park, Jeong-Min;Kim, Yong-Seok
    • Mycobiology
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    • v.34 no.4
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    • pp.230-235
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    • 2006
  • Fruiting bodies of Phellinus linteus were extracted by hot water and alkali methods. Sugar contents of PL-H (hot water extract) and PL-A (alkali water extract) were 81.1%, 37.4% and protein contents were 6.2%, 21.8%, respectively. Amino acid pattern showed that two extracts contained large amount of aspartic acid and alanine. Two extracts showed characteristic IR absorption pattern for glycosidic bond at $890\;cm^{-1}$. PL-H was divided two fractions by gel filtration chromatography and the molecular weights of each fraction were estimated to be about 10 kD and 225 kD, respectively and also PL-A was estimated 10 kD. Two extracts showed strong antitumor, immunomodulating and antioxidant activities, and were compared with commercialized glycopeptide anticancer drugs.

Elicitor-induced Phenylalanine-Ammonia Lyase, Cinnamic Acid 4-Hydroxylase and $rho-Coumaroyl$ transferase Activity in Ephedra Distachya Cultures

  • Song, Kyung-Sik;Yutaka Ebizuka
    • Archives of Pharmacal Research
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    • v.19 no.3
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    • pp.219-222
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    • 1996
  • Ephedra olistachya cultures have been known to accumulate $rho-coumaroylamino$ acids by elicitor treatment. Based on their chemical structures, the biosynthetic pathway of$rho-coumaroylamino$acids was postulated and phenylalanine ammonia-lyase (PAL), cinnamic acid 4-hydroxylase (4-CH) and p-coumaroyl CoA: D-Ala p-coumaroyltransferase ($rho-CT$) were supposed to be involved in the pathway. The time course inductions of these enzymes were investigated after treatment of yeast extract, yeast-derived mannan glycopeptide and D-Ala. They were detectable at only 4 hours and reached to their maximum level at 9 hours after onset of elicitor treatment. The activities of PAL and 4-CH were almost disappeared within 24 hours, however, that of $rho-CT$was remained up to 48 hours irrespective of the kind of elicitors. $rho-CT$ showed substrate specificity to D-Ala at crude enzyme extract level.

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Rapid Detection of Vancomycin-resistance Enterococci by SYBR Green Real-time PCR

  • Yang, Byoung-Seon
    • Korean Journal of Clinical Laboratory Science
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    • v.46 no.2
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    • pp.64-67
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    • 2014
  • Vancomycin-resistant Enterococci (VRE) are a leading cause of a nosocomial infection. While seven glycopeptide resistance genotypes have been found in Enterococci, vanA and vanB are the most common resistance genotypes. Aims of this study were to detect antibiotic susceptibilities of 23 Enterococcus spp, which broke out in a university hospital by the disk diffusion test, to investigate specific genes of vanA and vanB by conventional and real-time PCR. PCR for vanA and vanB was performed on 23 Enterococci, all 23 were positive for vanA type. This study reports the validation of a simple and rapid VRE detection method that can be easily incorporated into the daily routine of a clinical laboratory. Early detection of VRE strains, including those with susceptibility to Vancomycin, is of paramount clinical importance, as it allows a rapid initiation of strict infection control practices as well as a therapeutic guidance for a confirmed infection. The real-time PCR method is a rapid technique to detect vanA in Enterococci. It is simple and reliable for the rapid characterization of VRE.

The Evaluation of Teicoplanin Usage in a University Hospital (대학병원에서의 Teicoplanin의 사용 현황 조사 및 실태 평가)

  • Kim, Eun A;Oh, Jung Mi
    • Korean Journal of Clinical Pharmacy
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    • v.11 no.1
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    • pp.19-29
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    • 2001
  • Teicoplanin, a glycopeptide antibiotic, has potential for use as an alternative to vancomycin in the treatment of gram-positive bacterial infections. However, unlike vancomycin, there is a lack of study on teicoplanin's efficacy and safety and the guideline for its use is not available, yet. The objective of this study was to investigate and evaluate the pattern of teicoplanin usage in a university hospital. A retrospective study was performed on 72 adult patients, who took teicoplanin for 3 continuous days at D. University hospital from 1 January 1999 to 30 June 2000. The microorganisms treated with teicoplanin were methicillin-resistant Staphylocorcus aureus $(69\%)$, coagulase-negative Staphylococci $(12\%)$, Enterococcus $(4\%)$, vancomycin-resistant Enterococci $(2\%)$, Streptococci $(2\%)$, and Bacillus $(1\%)$. The types of infection treated with teicoplanin were surgical wound infection $(58\%)$, lower respiratory infection $(11\%)$, bactremia $(7\%)$, urinary tract infection $(5\%)$, pleural fluid infection $(4\%)$, and peritoneal fluid infection $(2\%)$. The mean duration of teicoplanin usage was 16.5 days and teicoplanin was used with 1.4 other antibiotics, which were aminoglycosides (isepamicin, amikacin, netilmicin, astromicin) or quinolones (ciprofloxacin, tosufloxacin) or the third generation cephalosporin (ceftazidime). Only 24 cases $(28.6\%)$ met with the criteria for the justification of use, and the rest of 60 cases $(71.4\%)$ did not meet the criteria. In 84 cases $(100\%)$, blood culture tests were performed prior to the initial dose of teicoplanin. In 83 cases $(99\%)$, serum creatinine were conducted before the initial doses. In 45 cases $(53.6\%)$, serum creatinine was monitored at least twice weekly. In 55 cases $(65.5\%)$, WBC was tested at least twice weekly. In 84 cases $(100\%)$, body temperature was monitored at least once per nursing shift. In 15 cases out of 56 cases, maximum temperature decreased at least 1 degree within 3 days of teicoplanin use. In 15 case out of 35 cases, WBC values were within the normal range after treatment. In 23 cases $(27.4\%)$, dosage regimen was appropriate. Drug-related adverse effects were reported in 13 cases. Nephrotoxicity (progressively increasing SCr. or sustained SCr increase of $\geq$0.5 mg/dl from baseline) was noted in five cases. Neutropenia (absolute neutrophil count <1,500 $cells/mm^3$) was noted in one case and eosinophilia (total eosinophil count >350 $cells/mm^3$) was noted in seven cases. A more strict control on use of teicoplanin is required, considering that teicoplanin is categorized as one of restricted antibiotics.

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