{"title":"Inhibition of <i>N</i>-Glycosylation towards Novel Anti-Cancer Chemotherapeutics.","authors":"Michio Kurosu","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":90605,"journal":{"name":"Journal of molecular pharmaceutics & organic process research","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223642/pdf/nihms935464.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36665736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01DOI: 10.4172/2329-9053.1000141
M. Kurosu
Cell surface polysaccharides play important roles in numerous biological processes in living organisms such as maintenance of outer membrane integrity, mediators of host-pathogen interactions, cell-celladhesion and recognition, protein folding, cell signalling, and trafficking of proteins translated within the rough endoplasmic reticulum (ER) to the Golgi. Furthermore, abnormal glycosylation of cell surface proteins takes place during which normal cells progress to a malignant neoplastic state [1]. Thus, the modification of cell surface glycosylation is a characteristic of many cancer cells [2-5]. Many of the recently developed tumor markers are carbohydrate antigens. Identification of cell type-specific or tissue-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems or diagnosis for certain cancers via immunodetection reagents [1]. On the other hand, anti-glycan antibodies have a limited application for cancer treatment, despite the fact that a great number of tumorassociated glycans have been identified with the help of modern glycomic approaches [6]. In the last two decades, a few monoclonal antibodies targeting ganglioside GD2 or GD3 and a cancer vaccine with N-glycolylated ganglioside GM3 have been developed into clinical trials. As such, changes and diversification of the expression profile of cell surface glycans based on the underlying glycobiology have received much attention from the scientific community [1]. Two of the most abundant forms of glycosylation occurring on proteins destined to be secreted or membrane-bound proteins are N-linked (to Asp (N), Nglycosylation) and mucin-type O-linked (to Ser/Thr, O-glycosylation). O-Linked glycosylation is an evolutionarily conserved protein modification found across species such as mammals, worms, insects, protozoa, and certain types of fungi, whereas N-linked glycosylation occurs in eukaryotes and widely in archaea, but very rarely in bacteria. Recent studies of cancer immunotherapy are based on immunogenicity of truncated O-glycan chains (e.g. Tn, sTn, T, and sLea/x). Despite the importance of N-linked glycans in transformation-associated glycosylation changes for normal cells to develop tumor cells, therapeutic antibodies against N-linked glycans have not yet been developed. It may largely be attributable to the lack of specificity of Nlinked glycans between normal and malignant cells. Abnormal (increased) branching of N-linked glycans has been observed in certain solid cancer cells. Altered glycosylation of N-linked glycans in cancers is typically associated with upregulation of β1,6-Nacetylyglucosaminyltransferase-5 (GnT5), enhancing β1,6-branching. Although it is an extremely challenging subject to discover drug-like glycosyltransferases to block the biosynthesis of specific branching processes in cancer cells, N-glycan biosynthesis can be terminated by inhibition of the first committed enzyme, dolichyl-phosphate Nacetylglucosaminephosphotransferase (DPAG
{"title":"Inhibition of N-Glycosylation towards Novel Anti-Cancer Chemotherapeutics.","authors":"M. Kurosu","doi":"10.4172/2329-9053.1000141","DOIUrl":"https://doi.org/10.4172/2329-9053.1000141","url":null,"abstract":"Cell surface polysaccharides play important roles in numerous biological processes in living organisms such as maintenance of outer membrane integrity, mediators of host-pathogen interactions, cell-celladhesion and recognition, protein folding, cell signalling, and trafficking of proteins translated within the rough endoplasmic reticulum (ER) to the Golgi. Furthermore, abnormal glycosylation of cell surface proteins takes place during which normal cells progress to a malignant neoplastic state [1]. Thus, the modification of cell surface glycosylation is a characteristic of many cancer cells [2-5]. Many of the recently developed tumor markers are carbohydrate antigens. Identification of cell type-specific or tissue-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems or diagnosis for certain cancers via immunodetection reagents [1]. On the other hand, anti-glycan antibodies have a limited application for cancer treatment, despite the fact that a great number of tumorassociated glycans have been identified with the help of modern glycomic approaches [6]. In the last two decades, a few monoclonal antibodies targeting ganglioside GD2 or GD3 and a cancer vaccine with N-glycolylated ganglioside GM3 have been developed into clinical trials. As such, changes and diversification of the expression profile of cell surface glycans based on the underlying glycobiology have received much attention from the scientific community [1]. Two of the most abundant forms of glycosylation occurring on proteins destined to be secreted or membrane-bound proteins are N-linked (to Asp (N), Nglycosylation) and mucin-type O-linked (to Ser/Thr, O-glycosylation). O-Linked glycosylation is an evolutionarily conserved protein modification found across species such as mammals, worms, insects, protozoa, and certain types of fungi, whereas N-linked glycosylation occurs in eukaryotes and widely in archaea, but very rarely in bacteria. Recent studies of cancer immunotherapy are based on immunogenicity of truncated O-glycan chains (e.g. Tn, sTn, T, and sLea/x). Despite the importance of N-linked glycans in transformation-associated glycosylation changes for normal cells to develop tumor cells, therapeutic antibodies against N-linked glycans have not yet been developed. It may largely be attributable to the lack of specificity of Nlinked glycans between normal and malignant cells. Abnormal (increased) branching of N-linked glycans has been observed in certain solid cancer cells. Altered glycosylation of N-linked glycans in cancers is typically associated with upregulation of β1,6-Nacetylyglucosaminyltransferase-5 (GnT5), enhancing β1,6-branching. Although it is an extremely challenging subject to discover drug-like glycosyltransferases to block the biosynthesis of specific branching processes in cancer cells, N-glycan biosynthesis can be terminated by inhibition of the first committed enzyme, dolichyl-phosphate Nacetylglucosaminephosphotransferase (DPAG","PeriodicalId":90605,"journal":{"name":"Journal of molecular pharmaceutics & organic process research","volume":"6 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70276928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-01Epub Date: 2015-07-22DOI: 10.4172/2329-9053.1000125
Nolé Tsabang, Stella Kadjob, Rose N Mballa, Clement G Yedjou, Nga Nnanga, Néhémie T Donfagsiteli, Alembert T Tchinda, Gabriel A Agbor, Claudine Ntsama, Paul B Tchounwou
A majority of Africans rely on traditional medicine as the primary form of health care. Yet most traditional medicine products have a short shelf life, especially for water-based formulations such as macerations, infusions and decoctions. Indeed, many of these water extracts become unfit for human consumption after five to seven days of conservation either because of the degradation or toxicity of active components, and/or the growth of pathogenic organisms. The purpose of this study was to describe and apply a new approach for the development of an improved traditional medicine (ITM) that is cheap, very efficient, not toxic, and easy to produce, and that can be conserved for a longer time without a significant loss of activity. Hence, Laportea ovalifolia was selected from an ethnobotanical prospection in all regions of Cameroon, and was used to prepare an oral hypoglycemic product. This preparation required 9 steps focused on the characterization of the plant species, and the standardization of the ethnopharmacological preparation by a multidisciplinary team of scientists with expertise in botany, ecology, pharmacognosy and pharmacology. Resultantly, four galenic formulations of hypoglycemic medications were produced. A relationship between these four formulations was described as follow: One spoon of oral suspension (10 ml)=one sachet of powder=2 tablets=3 capsules. Hence, our research provides new insight into a drug discovery approach that could alleviate the major problems affecting traditional medicine and enhance its effectiveness in addressing health care in developing and undeveloped countries.
{"title":"New Approach for the Development of Improved Traditional Medicine: Case of a Preparation of an Oral Hypoglycemic Medicine from <i>Laportea ovalifolia</i> (Schumach. & Thonn.) Chew. (Urticaceae).","authors":"Nolé Tsabang, Stella Kadjob, Rose N Mballa, Clement G Yedjou, Nga Nnanga, Néhémie T Donfagsiteli, Alembert T Tchinda, Gabriel A Agbor, Claudine Ntsama, Paul B Tchounwou","doi":"10.4172/2329-9053.1000125","DOIUrl":"10.4172/2329-9053.1000125","url":null,"abstract":"<p><p>A majority of Africans rely on traditional medicine as the primary form of health care. Yet most traditional medicine products have a short shelf life, especially for water-based formulations such as macerations, infusions and decoctions. Indeed, many of these water extracts become unfit for human consumption after five to seven days of conservation either because of the degradation or toxicity of active components, and/or the growth of pathogenic organisms. The purpose of this study was to describe and apply a new approach for the development of an improved traditional medicine (ITM) that is cheap, very efficient, not toxic, and easy to produce, and that can be conserved for a longer time without a significant loss of activity. Hence, <i>Laportea ovalifolia</i> was selected from an ethnobotanical prospection in all regions of Cameroon, and was used to prepare an oral hypoglycemic product. This preparation required 9 steps focused on the characterization of the plant species, and the standardization of the ethnopharmacological preparation by a multidisciplinary team of scientists with expertise in botany, ecology, pharmacognosy and pharmacology. Resultantly, four galenic formulations of hypoglycemic medications were produced. A relationship between these four formulations was described as follow: One spoon of oral suspension (10 ml)=one sachet of powder=2 tablets=3 capsules. Hence, our research provides new insight into a drug discovery approach that could alleviate the major problems affecting traditional medicine and enhance its effectiveness in addressing health care in developing and undeveloped countries.</p>","PeriodicalId":90605,"journal":{"name":"Journal of molecular pharmaceutics & organic process research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70276896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Misfolding and aggregation of proteins is a common thread linking a number of important human health problems. Particularly, recent studies highlighted increasing recognition of the public health importance of protein deposition diseases, including neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s (AD), Huntington’s and prion diseases and many other disorders [1]. Little progress has been made in the treatment of these diseases, due to a fundamental lack of knowledge of the protein self-assembly process. In fact, no effective therapeutic agents exist for Alzheimer’s disease, the most common neurodegenerative disease of aging. Understanding the mechanisms underlying selfassembly into nano-aggregates would facilitate the development of efficient therapeutic and diagnostic tools for these devastating diseases.
{"title":"Nanoimaging for Molecular Pharmaceutics of Alzheimer's and other Neurodegenerative Disorders.","authors":"Yuri L Lyubchenko","doi":"10.4172/jmpopr.1000e107","DOIUrl":"https://doi.org/10.4172/jmpopr.1000e107","url":null,"abstract":"Misfolding and aggregation of proteins is a common thread linking a number of important human health problems. Particularly, recent studies highlighted increasing recognition of the public health importance of protein deposition diseases, including neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s (AD), Huntington’s and prion diseases and many other disorders [1]. Little progress has been made in the treatment of these diseases, due to a fundamental lack of knowledge of the protein self-assembly process. In fact, no effective therapeutic agents exist for Alzheimer’s disease, the most common neurodegenerative disease of aging. Understanding the mechanisms underlying selfassembly into nano-aggregates would facilitate the development of efficient therapeutic and diagnostic tools for these devastating diseases.","PeriodicalId":90605,"journal":{"name":"Journal of molecular pharmaceutics & organic process research","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/jmpopr.1000e107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32972032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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