Molecular design and synthesis of novel peptides from amphibians skin acting as inhibitors of cholinesterase enzymes
Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. There are two types of cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which differ in their distribution in the body. Currently, cholinesterase inhibitors (ChEI) re...
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| Veröffentlicht in: | Journal of peptide science 2017-03, Vol.23 (3), p.236-244 |
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| creator | Siano, Alvaro Garibotto, Francisco F. Andujar, Sebastian A. Baldoni, Hector A. Tonarelli, Georgina G. Enriz, Ricardo D. |
| description | Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. There are two types of cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which differ in their distribution in the body. Currently, cholinesterase inhibitors (ChEI) represent the treatment of choice for Alzheimer's disease (AD). In this paper, we report the synthesis and inhibitory effect on both enzymes of four new peptides structurally related to P1‐Hp‐1971 (amphibian skin peptide found in our previous work. Sequence: TKPTLLGLPLGAGPAAGPGKR‐NH2). The bioassay data and cytotoxicity test show that some of the compounds possess a significant AChE and BChE inhibition and no toxic effect. The present work demonstrates that diminution of the size of the original peptide could potentially result in new compounds with significant cholinesterase inhibition activity, although it appears that there is an optimal size for the sequence. We also conducted an exhaustive molecular modeling study to better understand the mechanism of action of these compounds by combining docking techniques with molecular dynamics simulations on BChE. This is the first report about amphibian peptides and the second one of natural peptides with ChE inhibitory activity. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. Currently, cholinesterase inhibitors represent the treatment of choice for Alzheimer's disease. In this paper, we report the synthesis and inhibitory effect of novel peptides from amphibian's skin acting as inhibitors of cholinesterase enzymes. |
| doi_str_mv | 10.1002/psc.2974 |
| format | Article |
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Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. Currently, cholinesterase inhibitors represent the treatment of choice for Alzheimer's disease. In this paper, we report the synthesis and inhibitory effect of novel peptides from amphibian's skin acting as inhibitors of cholinesterase enzymes.</description><identifier>ISSN: 1075-2617</identifier><identifier>EISSN: 1099-1387</identifier><identifier>DOI: 10.1002/psc.2974</identifier><identifier>PMID: 28150445</identifier><identifier>CODEN: JPSIEI</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Acetylcholinesterase ; Acetylcholinesterase - chemistry ; Alzheimer's disease ; Amino Acid Sequence ; Amphibian Proteins - chemistry ; Amphibians ; Animals ; Anura ; Bioassays ; butyrylcholinesterase ; Butyrylcholinesterase - chemistry ; Chemical synthesis ; Cholinesterase ; Cholinesterase inhibitors ; Cholinesterase Inhibitors - chemical synthesis ; Cholinesterase Inhibitors - chemistry ; Computer simulation ; Current distribution ; Cytotoxicity ; docking ; Drug Design ; Enzymes ; Humans ; Hydrolysis ; Inhibition ; Inhibitors ; Molecular docking ; Molecular Docking Simulation ; Molecular dynamics ; Molecular Dynamics Simulation ; Molecular modelling ; Neurodegenerative diseases ; peptide ; Peptides ; Peptides - chemical synthesis ; Peptides - chemistry ; Reptiles & amphibians ; Skin ; Solid-Phase Synthesis Techniques - methods ; Structure-Activity Relationship ; Toxicity testing</subject><ispartof>Journal of peptide science, 2017-03, Vol.23 (3), p.236-244</ispartof><rights>Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4804-a2dd14a8cf685fa75c5b9b9fc7f551da0595596bf40b1d7a4f7937d29faa68db3</citedby><cites>FETCH-LOGICAL-c4804-a2dd14a8cf685fa75c5b9b9fc7f551da0595596bf40b1d7a4f7937d29faa68db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpsc.2974$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpsc.2974$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28150445$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siano, Alvaro</creatorcontrib><creatorcontrib>Garibotto, Francisco F.</creatorcontrib><creatorcontrib>Andujar, Sebastian A.</creatorcontrib><creatorcontrib>Baldoni, Hector A.</creatorcontrib><creatorcontrib>Tonarelli, Georgina G.</creatorcontrib><creatorcontrib>Enriz, Ricardo D.</creatorcontrib><title>Molecular design and synthesis of novel peptides from amphibians skin acting as inhibitors of cholinesterase enzymes</title><title>Journal of peptide science</title><addtitle>J Pept Sci</addtitle><description>Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. There are two types of cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which differ in their distribution in the body. Currently, cholinesterase inhibitors (ChEI) represent the treatment of choice for Alzheimer's disease (AD). In this paper, we report the synthesis and inhibitory effect on both enzymes of four new peptides structurally related to P1‐Hp‐1971 (amphibian skin peptide found in our previous work. Sequence: TKPTLLGLPLGAGPAAGPGKR‐NH2). The bioassay data and cytotoxicity test show that some of the compounds possess a significant AChE and BChE inhibition and no toxic effect. The present work demonstrates that diminution of the size of the original peptide could potentially result in new compounds with significant cholinesterase inhibition activity, although it appears that there is an optimal size for the sequence. We also conducted an exhaustive molecular modeling study to better understand the mechanism of action of these compounds by combining docking techniques with molecular dynamics simulations on BChE. This is the first report about amphibian peptides and the second one of natural peptides with ChE inhibitory activity. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. Currently, cholinesterase inhibitors represent the treatment of choice for Alzheimer's disease. In this paper, we report the synthesis and inhibitory effect of novel peptides from amphibian's skin acting as inhibitors of cholinesterase enzymes.</description><subject>Acetylcholinesterase</subject><subject>Acetylcholinesterase - chemistry</subject><subject>Alzheimer's disease</subject><subject>Amino Acid Sequence</subject><subject>Amphibian Proteins - chemistry</subject><subject>Amphibians</subject><subject>Animals</subject><subject>Anura</subject><subject>Bioassays</subject><subject>butyrylcholinesterase</subject><subject>Butyrylcholinesterase - chemistry</subject><subject>Chemical synthesis</subject><subject>Cholinesterase</subject><subject>Cholinesterase inhibitors</subject><subject>Cholinesterase Inhibitors - chemical synthesis</subject><subject>Cholinesterase Inhibitors - chemistry</subject><subject>Computer simulation</subject><subject>Current distribution</subject><subject>Cytotoxicity</subject><subject>docking</subject><subject>Drug Design</subject><subject>Enzymes</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Inhibition</subject><subject>Inhibitors</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>Molecular modelling</subject><subject>Neurodegenerative diseases</subject><subject>peptide</subject><subject>Peptides</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - chemistry</subject><subject>Reptiles & amphibians</subject><subject>Skin</subject><subject>Solid-Phase Synthesis Techniques - methods</subject><subject>Structure-Activity Relationship</subject><subject>Toxicity testing</subject><issn>1075-2617</issn><issn>1099-1387</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1rFTEQhoMotlahv6AEvPFma7KbbJLLcvALKgq21yGbj57U3WSb2VWOv96cflgQ9GpmmGfeGeZF6JiSU0pI-3YGe9oqwZ6gQ0qUamgnxdN9LnjT9lQcoBcA14TUHu-fo4NWUk4Y44do-ZxHb9fRFOw8xKuETXIYdmnZ1hJwDjjlH37Es5-XWBEcSp6wmeZtHKJJgOF7rEN2iekKG8Ax7RtLLrezdpvHmDwsvhjw2Kdfu8nDS_QsmBH8q_t4hC7fv7vYfGzOv3z4tDk7byyThDWmdY4yI23oJQ9GcMsHNahgReCcOkO44lz1Q2BkoE4YFoTqhGtVMKaXbuiO0Js73bnkm7VeoacI1o-jST6voKkUon6il31FX_-FXue1pHqdpop0hLeUdP-lpGh7ITvJHtfakgGKD3oucTJlpynRe7909Uvv_aroyb3gOkze_QEfDKpAcwf8jKPf_VNIf_22uRX8DffSn-U</recordid><startdate>201703</startdate><enddate>201703</enddate><creator>Siano, Alvaro</creator><creator>Garibotto, Francisco F.</creator><creator>Andujar, Sebastian A.</creator><creator>Baldoni, Hector A.</creator><creator>Tonarelli, Georgina G.</creator><creator>Enriz, Ricardo D.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope></search><sort><creationdate>201703</creationdate><title>Molecular design and synthesis of novel peptides from amphibians skin acting as inhibitors of cholinesterase enzymes</title><author>Siano, Alvaro ; Garibotto, Francisco F. ; Andujar, Sebastian A. ; Baldoni, Hector A. ; Tonarelli, Georgina G. ; Enriz, Ricardo D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4804-a2dd14a8cf685fa75c5b9b9fc7f551da0595596bf40b1d7a4f7937d29faa68db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetylcholinesterase</topic><topic>Acetylcholinesterase - chemistry</topic><topic>Alzheimer's disease</topic><topic>Amino Acid Sequence</topic><topic>Amphibian Proteins - chemistry</topic><topic>Amphibians</topic><topic>Animals</topic><topic>Anura</topic><topic>Bioassays</topic><topic>butyrylcholinesterase</topic><topic>Butyrylcholinesterase - chemistry</topic><topic>Chemical synthesis</topic><topic>Cholinesterase</topic><topic>Cholinesterase inhibitors</topic><topic>Cholinesterase Inhibitors - chemical synthesis</topic><topic>Cholinesterase Inhibitors - chemistry</topic><topic>Computer simulation</topic><topic>Current distribution</topic><topic>Cytotoxicity</topic><topic>docking</topic><topic>Drug Design</topic><topic>Enzymes</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Inhibition</topic><topic>Inhibitors</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Molecular dynamics</topic><topic>Molecular Dynamics Simulation</topic><topic>Molecular modelling</topic><topic>Neurodegenerative diseases</topic><topic>peptide</topic><topic>Peptides</topic><topic>Peptides - chemical synthesis</topic><topic>Peptides - chemistry</topic><topic>Reptiles & amphibians</topic><topic>Skin</topic><topic>Solid-Phase Synthesis Techniques - methods</topic><topic>Structure-Activity Relationship</topic><topic>Toxicity testing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siano, Alvaro</creatorcontrib><creatorcontrib>Garibotto, Francisco F.</creatorcontrib><creatorcontrib>Andujar, Sebastian A.</creatorcontrib><creatorcontrib>Baldoni, Hector A.</creatorcontrib><creatorcontrib>Tonarelli, Georgina G.</creatorcontrib><creatorcontrib>Enriz, Ricardo D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of peptide science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siano, Alvaro</au><au>Garibotto, Francisco F.</au><au>Andujar, Sebastian A.</au><au>Baldoni, Hector A.</au><au>Tonarelli, Georgina G.</au><au>Enriz, Ricardo D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular design and synthesis of novel peptides from amphibians skin acting as inhibitors of cholinesterase enzymes</atitle><jtitle>Journal of peptide science</jtitle><addtitle>J Pept Sci</addtitle><date>2017-03</date><risdate>2017</risdate><volume>23</volume><issue>3</issue><spage>236</spage><epage>244</epage><pages>236-244</pages><issn>1075-2617</issn><eissn>1099-1387</eissn><coden>JPSIEI</coden><abstract>Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. There are two types of cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which differ in their distribution in the body. Currently, cholinesterase inhibitors (ChEI) represent the treatment of choice for Alzheimer's disease (AD). In this paper, we report the synthesis and inhibitory effect on both enzymes of four new peptides structurally related to P1‐Hp‐1971 (amphibian skin peptide found in our previous work. Sequence: TKPTLLGLPLGAGPAAGPGKR‐NH2). The bioassay data and cytotoxicity test show that some of the compounds possess a significant AChE and BChE inhibition and no toxic effect. The present work demonstrates that diminution of the size of the original peptide could potentially result in new compounds with significant cholinesterase inhibition activity, although it appears that there is an optimal size for the sequence. We also conducted an exhaustive molecular modeling study to better understand the mechanism of action of these compounds by combining docking techniques with molecular dynamics simulations on BChE. This is the first report about amphibian peptides and the second one of natural peptides with ChE inhibitory activity. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Cholinesterases are a family of enzymes that catalyze the hydrolysis of neurotransmitter acetylcholine. Currently, cholinesterase inhibitors represent the treatment of choice for Alzheimer's disease. In this paper, we report the synthesis and inhibitory effect of novel peptides from amphibian's skin acting as inhibitors of cholinesterase enzymes.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28150445</pmid><doi>10.1002/psc.2974</doi><tpages>9</tpages></addata></record> |
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| subjects | Acetylcholinesterase Acetylcholinesterase - chemistry Alzheimer's disease Amino Acid Sequence Amphibian Proteins - chemistry Amphibians Animals Anura Bioassays butyrylcholinesterase Butyrylcholinesterase - chemistry Chemical synthesis Cholinesterase Cholinesterase inhibitors Cholinesterase Inhibitors - chemical synthesis Cholinesterase Inhibitors - chemistry Computer simulation Current distribution Cytotoxicity docking Drug Design Enzymes Humans Hydrolysis Inhibition Inhibitors Molecular docking Molecular Docking Simulation Molecular dynamics Molecular Dynamics Simulation Molecular modelling Neurodegenerative diseases peptide Peptides Peptides - chemical synthesis Peptides - chemistry Reptiles & amphibians Skin Solid-Phase Synthesis Techniques - methods Structure-Activity Relationship Toxicity testing |
| title | Molecular design and synthesis of novel peptides from amphibians skin acting as inhibitors of cholinesterase enzymes |
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