• Archives of Pharmacal Research
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• 제4권2호
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• pp.99-107
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• 1981

To investigate the protein binding characteristics of ibuprofenlysine, the effects of drub conentration, pH, ionic strength and protein concentration on the binding of drug to protein concentration on the binding of drug to protein were studied by fluorescence probe method. The conformational change of protein was investigated by circular dichroism (CD) measurement. As the concentration of drug increases, the association constant decreases. These may be due to complex formation of the probe and drug, or the interaction of the protein-probe complex and drug. The association constant for ibuprofenlysine increased with increasing protein concentration. These finding suggest a sharing of one ibuprofenlysine molecule by more than one protein molecule in the binding. The binding between ibuprofenlysine and protein was dependent on pH and ionic strength. It seems that both hydrophobic binding and some electrostatic forces are involved in the binding of ibuprofenlysing to protein.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1996년도 정기총회 및 학술발표회
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• pp.37-37
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• 1996

Tenecin fragments are antimicrobial and antifungal peptide from Tenebrio molitor with highly positive charged amino acid residues. To elucidate their membrane selectivity and molecular mechanism, various forms of tenecin fragments were synthesized, and their interaction with acidic phospholipid, Gram (+), fungal and human erythrocyte membrane were investigated by ANTS/DPX leakage, membrane binding and fusion assay. (omitted)

• 인터넷정보학회논문지
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• 제15권4호
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• pp.21-31
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• 2014

단백질 의약품 산업이 성장함에 따라 단백질 의약품 개발 시 단백질 정보는 필수적으로 인식 되고 있다. 단백질 정보 서비스를 제공하는 대표적인 바이오데이터 센터로는 미국의 NCBI, PDB, 유럽의 EMBL, 일본의 DDBJ 등이 있으며, 각 센터별로 특화된 단백질 정보들이 제공되고 있다. 사용자가 원하는 단백질 정보를 얻기 위해서는 독립된 단백질 정보를 검색하고 이를 통합하고 분석해야하며, 보다 편리하게 접근할 수 있도록 대표적인 데이터 센터 혹은 소규모 프로젝트 별로 바이오데이터에 대한 다양한 웹서비스가 연구 개발되고 있다. 단백질 의약품 정보 서비스에 대한 필요성이 높아지면서 캐나다의 DrugBank, 미국의 GDSC 등에서 의약품 정보와 단백질 데이터를 통합하여 서비스하고 있다. 하지만 사용자가 요구하는 다양한 단백질 정보를 반영하지 못하는 실정이다. 국내의 경우 바이오인포매틱스 인프라가 부족하고, 단백질 의약품 정보 서비스 또한 의약품의 기본 정보와 유통정보만을 제공하는 것에 한정되어 있다. 본 연구에서는 기존 서비스의 한계를 벗어난 한국형 단백질 의약품 전용 서비스 설계를 위한 사전 연구로 기존 대표적 데이터베이스에서는 적용하고 있지 않은 단백질 특성정보필드들을 제시하고 이에 대한 유용성 평가를 전문 종사자를 대상으로 진행하여 기존 바이오데이터베이스의 단백질 정보 필드와 비교하였다. 그 결과 본 연구에서 제시한 단백질 특성정보필드들이 단백질 의약품 정보 서비스에 요구되는 유용한 데이터 필드임을 검증하였다.

• International Journal of Industrial Entomology and Biomaterials
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• 제3권1호
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• pp.1-6
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• 2001

Silk protein has been investigated by many researchers to apply to biomedical field. We reviewed biomedical applications of silk protein such as matrix of wound dressing and drug delivery system. Since silk fibroin/ poly (ethylene glycol) (PEG) semi-interpenetrating polymer networks showed good mechanical properties and wound healing phenomena, it can be used as wound dressing materials. Sericin nanoparticles pre- pared by conjugation with PEG and silk protein/ poloxamer mixture gel are expected to become a deliv- ery as matrix for hydrophobic drug.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.572-584
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• 2002

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.

• Journal of Microbiology and Biotechnology
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• 제18권5호
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• pp.845-851
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• 2008

TolC is an outer membrane porin protein and an essential component of drug efflux and type-I secretion systems in Gram-negative bacteria. TolC comprises a periplasmic $\alpha$-helical barrel domain and a membrane-embedded $\beta$-barrel domain. TdeA, a functional and structural homolog of TolC, is required for toxin and drug export in the pathogenic oral bacterium Actinobacillus actinomycetemcomitans. Here, we report the expression of the periplasmic domain of TdeA as a soluble protein by substitution of the membrane-embedded domain with short linkers, which enabled us to purify the protein in the absence of detergent. We confirmed the structural integrity of the TdeA periplasmic domain by size-exclusion chromatography, circular dichroism spectroscopy, and electron microscopy, which together showed that the periplasmic domain of the TolC protein family fold correctly on its own. We further demonstrated that the periplasmic domain of TdeA interacts with peptidoglycans of the bacterial cell wall, which supports the idea that completely folded TolC family proteins traverse the peptidoglycan layer to interact with inner membrane transporters.

• Genomics & Informatics
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• 제21권1호
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• pp.5.1-5.13
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• 2023

Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.

• Genomics & Informatics
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• 제18권4호
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• pp.43.1-43.13
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• 2020

The coronavirus disease 2019 is a contagious disease and had caused havoc throughout the world by creating widespread mortality and morbidity. The unavailability of vaccines and proper antiviral drugs encourages the researchers to identify potential antiviral drugs to be used against the virus. The presence of RNA binding domain in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be a potential drug target, which serves multiple critical functions during the viral life cycle, especially the viral replication. Since vaccine development might take some time, the identification of a drug compound targeting viral replication might offer a solution for treatment. The study analyzed the phylogenetic relationship of N protein sequence divergence with other 49 coronavirus species and also identified the conserved regions according to protein families through conserved domain search. Good structural binding affinities of a few natural and/or synthetic phytocompounds or drugs against N protein were determined using the molecular docking approaches. The analyzed compounds presented the higher numbers of hydrogen bonds of selected chemicals supporting the drug-ability of these compounds. Among them, the established antiviral drug glycyrrhizic acid and the phytochemical theaflavin can be considered as possible drug compounds against target N protein of SARS-CoV-2 as they showed lower binding affinities. The findings of this study might lead to the development of a drug for the SARS-CoV-2 mediated disease and offer solution to treatment of SARS-CoV-2 infection.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3631-3636
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• 2012

Objective: To determine whether silence of $PKC-{\alpha}$ expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer. Methods: We measured gene and protein expression of MDR1 and $PKC-{\alpha}$ in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking $PKC-{\alpha}$ by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests. Results: The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and $PKC-{\alpha}$ than their counterpart sensitive cell line, OV1228. SiRNA depressed $PKC-{\alpha}$ gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells. Conclusion: These results indicated that decreasing $PKC-{\alpha}$ expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of $PKC-{\alpha}$ and MDR1. A new siRNA-based therapeutic strategy targeting $PKC-{\alpha}$ gene could be designed to overcome the chemoresistance of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4995-5000
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• 2014

Background: Cancer constitutes a key pressure on public health regardless of the economy state in different countries. As a kind of highly malignant epithelial tumor, lacrimal gland adenoid cystic carcinoma can occur in any part of the body, such as salivary gland, submandibular gland, trachea, lung, breast, skin and lacrimal gland. Chemotherapy is one of the key treatment techniques, but drug resistance, especially MDR, seriously blunts its effects. As an element of the 60S large ribosomal subunit, the ribosomal protein L39-L gene appears to be documented specifically in the human testis and many human cancer samples of different origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible lacrimal gland adenoid cystic carcinoma cells was seperated, and real time quantitative RT-PCR were used to reveal transcription differences between amycin resistant and susceptible strains of lacrimal gland adenoid cystic carcinoma cells. Viability assays were used to present the amycin resistance difference in a RPL39-L transfected lacrimal gland adenoid cystic carcinoma cell line as compared to control vector and null-transfected lacrimal gland adenoid cystic carcinoma cell lines. Results: The ribosomal protein L39-L transcription level was 6.5-fold higher in the drug-resistant human lacrimal gland adenoid cystic carcinoma cell line than in the susceptible cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells revealed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions: The ribosomal protein L39-L gene could possibly have influence on the drug resistance mechanism of lacrimal gland adenoid cystic carcinoma cells.