• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XII)
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• pp.484-488
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• 2003

고체상 site-specific mono-PEGylation 공정은 액체상 PEGylation 공정에서 나타날 수 있는 무작위적인 multi-PEGylation 문제점을 해결하고, 또한 고체상에서 PEGylation을 수행함으로써 액체상 PEGylation 공정에서 필요한 분리정제 단계를 줄일 수 있음을 제시하였다.

• KSBB Journal
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• 제21권2호
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• pp.133-139
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• 2006

혈액 내 순환시 안정성 향상과 면역원성의 감소를 위해, rhIFN-${\alpha}$-2a은 N-terminus의 ${\alpha}$-아민기에 mPEG aldehyde를 solid-phase PEGylation 시킨다. CM-Sepharose와 같은 양이온 교환수지가 고체 지지체로 사용되었다. Mono-PEGylate는 양이온 교환 수지에서 unmodified 단백질과 분리되어 용출된다. Site-srecific PEGylation과 mono-PEGylate의 분리가 한 단계의 공정으로 얻어진다는 점은 solid-phase PEGylation의 이점을 뒷받침해준다. 위치 특이성은 peptide digest의 질량 분석과 Edman degradation을 이용한 N-terminal sequencing에 의해 확인하였다. Mono-PEGylate는 항바이러스 활성과 면역원성의 감소를 나타내고, 감소 정도는 결합되는 mPEG의 분자량에 비례한다. Trypsin 저항성과 온도 안정성은 mono-PEGylation에 의해 두드러지게 개선되었다. Solid-phase PEGylation을 통해 종래의 액상 반응에서 나타날 수 있는 재현성 낮은 반응, 부 반응물 생성, 부 반응물 제거 공정 등의 단점을 극복할 수 있었다. 그러나 solid-phase PEGylation의 문제점인 액상 반응에 비교하여 많은 양의 PEG를 사용하여야 한다는 점은 개선되어야 한다.

• KSBB Journal
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• 제26권4호
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• pp.293-299
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• 2011

PEGylation, the attachment of polyethylene glycol (PEG) to proteins, is currently main technology for improving efficacy of protein drugs. This technology can prolong the plasma half-life, augment the in vivo stability, and diminish the immunogenicity of therapeutic proteins. Therefore, PEGylated proteins have the enhanced therapeutic efficacy and the reduced undesirable effects versus their native therapeutics. Since the first PEGylated protein product appeared on the market in the early 1990s, currently ten PEGylated protein products have been launched. These marketed drug products have proved the applicability and safety of the PEGylation technology. This review presents overview of PEGylation technology and addresses characteristics of PEGylation methods applied for the development of several protein drugs.

• KSBB Journal
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• 제20권5호
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• pp.338-340
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• 2005

변성제 (urea)와 환원제에 의해 완전히 풀린 상태의 lipase도 PEG에 의해 수식되는 것을 관찰하였다. 또한 mPEG-aldehyde로 수식된 mono-PEGylate과 di-PEGylate을 변성제와 환원제를 이용해 unfolding 시킨 후 희석에 의한 재접힘 시킨 결과, lipase에 공유결합된 PEG 분자는 재접힘 수율에 거의 영향을 미치지 않는 것으로 나타났다. 따라서 내포체 단백질을 대상으로 변성된 상태에서 PEGylation시킨 후 in vitro 재접힘 공정을 통해 PEGylation된 상태의 재생된 단백질을 회수할 수 있는 통합공정의 타당성을 제시하였다.

• Journal of Pharmaceutical Investigation
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• 제30권2호
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• pp.73-83
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• 2000

Polyethylene glycol (PEG) is a water soluble, biocompatible, non-toxic polymer and PEGylation is a well established technique for the modification of therapeutic proteins and peptides. PEG-protein drugs have been extensively studies in relation to therapies for various diseases: cancer, inflammation and others. The covalent attachment of PEG to proteins and peptides prolonged plasma half-life, reduced antigenicity and immunogenicity, increased thermal and mechanical stability, and prevented degradation by enzymes. Several chemical groups for general and site specific conjugation have been exploited to activate PEG for amino group, carboxyl group, and cysteine groups. PEGylation of many proteins and peptides have been studied to enhance their properties for the potential uses. Also, the different positional isomers in several PEG-proteins have shown the difference in vivo stability and biological indicating that the site of PEG molecule attachment is one of the important factor to develop PEG-proteins as potential therapeutic agents.

• International Journal of Industrial Entomology and Biomaterials
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• 제20권2호
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• pp.87-91
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• 2010

Silk fibroin model peptide, alanine pentamer was synthesized through solid-phase method and modified with poly(ethylene glycol). Nuclear magnetic resonance spectrometry and Fourier-transform infrared spectroscopy showed the conformation of alanine pentamer, $\beta$-sheet structure and random coil conformation were not changed with PEGylation. Differential scanning calorimetry showed that relatively strong exothermic peak around $180^{\circ}C$ by PEGylation. No cytotoxicity of PEGylated pentamer was observed by L929 cell proliferation test.

• KSBB Journal
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• 제17권1호
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• pp.33-37
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• 2002

PLGA 미립구로부터 G-CSF의 방출 거동 양상을 향상 시키기 위하여 G-CSF를 분자량 5000인 methoxy polyethylene glycol-aldehyde로 PEGylation 시켰다. 대부분의 G-CSF는 mono-PEGylation 되었으며, 이를 SDS-PAGE, HPLC, 및 펩타이드 지도 분석을 통해 확인하였다. W/O/W 방법을 사용하여 G-CSF 및 PEGylated G-CSF의 PLGA 미립구를 제조하였으며, 이때 봉입율은 높은 상태였다. 미립구내로 더 많은 G-CSF를 봉입하기 위하여 액상의 G-CSF 및 PEGylated G-CSF을 농축하였고 native gel과 gel filtration 크로마토 그래피를 통하여 단백질이 안정함을 확인하였다. 이렇게 제조한 PLGA 봉입체의 in vitro 방출 거동을 조사한 결과 PEGylated G-CSF는 native G-CSF에 비하여 더 오랜 시간 동안 방출이 지속되었고 최대 방출량도 증가하였다.

• Journal of Microbiology and Biotechnology
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• 제32권9호
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• pp.1209-1216
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• 2022

To better understand the effects of PEGylation and biotinylation on the delivery efficiency of proteins, the cationic protein lysozyme (LZ) and anionic protein bovine serum albumin (BSA) were chemically conjugated with poly(ethylene glycol) (PEG) and biotin-PEG to primary amine groups of proteins using N-hydroxysuccinimide reactions. Four types of protein conjugates were successfully prepared: PEGylated LZ (PEG-LZ), PEGylated BSA (PEG-BSA), biotin-PEG-conjugated LZ (Bio-PEG-LZ), and biotin-PEG-conjugated BSA (Bio-PEG-BSA). PEG-LZ and Bio-PEG-LZ exhibited a lower intracellular uptake than that of LZ in A549 human lung cancer cells (in a two-dimensional culture). However, Bio-PEG-BSA showed significantly improved intracellular delivery as compared to that of PEG-BSA and BSA, probably because of favorable interactions with cells via biotin receptors. For A549/fibroblast coculture spheroids, PEG-LZ and PEG-BSA exhibited significantly decreased tissue penetration as compared with that of unmodified proteins. However, Bio-PEG-BSA showed tissue penetration comparable to that of unmodified BSA. In addition, citraconlyated LZ (Cit-LZ) showed reduced spheroid penetration as compared to that of LZ, probably owing to a decrease in protein charge. Taken together, chemical conjugation of targeting ligands-PEG to anionic proteins could be a promising strategy to improve intracellular delivery and in vivo activity, whereas modifications of cationic proteins should be more delicately designed.

• 미생물과산업
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• 제33권3호
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• pp.11-13
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• 2007

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.77-79
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• 2002