Peptide‐Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis‐Like Inflammation
Peptide‐drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increase...
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| creator | Bae, Do Hyun Bae, Hayeon Yu, Hyung‐Seok Dorjsembe, Banzragch No, Young Hyun Kim, Taejung Kim, Nam Hyeong Kim, Jin‐Woo Kim, Jiyool Lee, Bok‐Soo Kim, Ye Ji Park, Seongchan Khaleel, Zinah Hilal Sa, Deok Hyang Lee, Eui‐Chul Lee, Jaecheol Ham, Jungyeob Kim, Jin‐Chul Kim, Yong Ho |
| description | Peptide‐drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, physicochemical criteria based on cell‐penetrating peptides are employed to design transcellular peptides derived from an antimicrobial peptides library. Among the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, it is found that 6‐Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti‐inflammatory PDC. The transcellular PDC (SDT7‐conjugated with PAR, named TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular PDCs (TDCs) as a promising approach for the treatment of inflammatory skin disorders.
Transcellular peptides (SDTs) derived from antimicrobial peptides are designed based on cell‐penetrating peptides for efficient delivery through the skin barrier. 6‐Paradol (PAR) is conjugated with SDT7 to treat psoriatic skin inflammation by inhibiting phosphodiesterase 4. The transcellular peptide‐drug conjugate (TM5) exhibits superior efficacy in psoriasis mouse models suggesting a promise for treating inflammatory skin disorders. |
| doi_str_mv | 10.1002/adhm.202303480 |
| format | Article |
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Transcellular peptides (SDTs) derived from antimicrobial peptides are designed based on cell‐penetrating peptides for efficient delivery through the skin barrier. 6‐Paradol (PAR) is conjugated with SDT7 to treat psoriatic skin inflammation by inhibiting phosphodiesterase 4. The transcellular peptide‐drug conjugate (TM5) exhibits superior efficacy in psoriasis mouse models suggesting a promise for treating inflammatory skin disorders.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202303480</identifier><identifier>PMID: 38421096</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Antimicrobial peptides ; anti‐inflammation ; Bioavailability ; Cell permeability ; Conjugates ; Drug delivery ; Drug delivery systems ; Drug development ; ginger‐driven compounds ; Peptides ; peptide‐drug conjugates ; Permeability ; Pharmacology ; Phosphodiesterase IV ; Psoriasis ; skin barrier ; Skin diseases ; transcellular peptide</subject><ispartof>Advanced healthcare materials, 2024-06, Vol.13 (15), p.e2303480-n/a</ispartof><rights>2024 Wiley‐VCH GmbH</rights><rights>This article is protected by copyright. All rights reserved.</rights><rights>2024 Wiley‐VCH GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3280-ba28775345907909916188631a52ee7c8af053130aba19327c372ed68ba20f3f3</cites><orcidid>0000-0002-9106-3298</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202303480$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202303480$$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/38421096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bae, Do Hyun</creatorcontrib><creatorcontrib>Bae, Hayeon</creatorcontrib><creatorcontrib>Yu, Hyung‐Seok</creatorcontrib><creatorcontrib>Dorjsembe, Banzragch</creatorcontrib><creatorcontrib>No, Young Hyun</creatorcontrib><creatorcontrib>Kim, Taejung</creatorcontrib><creatorcontrib>Kim, Nam Hyeong</creatorcontrib><creatorcontrib>Kim, Jin‐Woo</creatorcontrib><creatorcontrib>Kim, Jiyool</creatorcontrib><creatorcontrib>Lee, Bok‐Soo</creatorcontrib><creatorcontrib>Kim, Ye Ji</creatorcontrib><creatorcontrib>Park, Seongchan</creatorcontrib><creatorcontrib>Khaleel, Zinah Hilal</creatorcontrib><creatorcontrib>Sa, Deok Hyang</creatorcontrib><creatorcontrib>Lee, Eui‐Chul</creatorcontrib><creatorcontrib>Lee, Jaecheol</creatorcontrib><creatorcontrib>Ham, Jungyeob</creatorcontrib><creatorcontrib>Kim, Jin‐Chul</creatorcontrib><creatorcontrib>Kim, Yong Ho</creatorcontrib><title>Peptide‐Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis‐Like Inflammation</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Peptide‐drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, physicochemical criteria based on cell‐penetrating peptides are employed to design transcellular peptides derived from an antimicrobial peptides library. Among the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, it is found that 6‐Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti‐inflammatory PDC. The transcellular PDC (SDT7‐conjugated with PAR, named TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular PDCs (TDCs) as a promising approach for the treatment of inflammatory skin disorders.
Transcellular peptides (SDTs) derived from antimicrobial peptides are designed based on cell‐penetrating peptides for efficient delivery through the skin barrier. 6‐Paradol (PAR) is conjugated with SDT7 to treat psoriatic skin inflammation by inhibiting phosphodiesterase 4. The transcellular peptide‐drug conjugate (TM5) exhibits superior efficacy in psoriasis mouse models suggesting a promise for treating inflammatory skin disorders.</description><subject>Animal models</subject><subject>Antimicrobial peptides</subject><subject>anti‐inflammation</subject><subject>Bioavailability</subject><subject>Cell permeability</subject><subject>Conjugates</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drug development</subject><subject>ginger‐driven compounds</subject><subject>Peptides</subject><subject>peptide‐drug conjugates</subject><subject>Permeability</subject><subject>Pharmacology</subject><subject>Phosphodiesterase IV</subject><subject>Psoriasis</subject><subject>skin barrier</subject><subject>Skin diseases</subject><subject>transcellular 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Nam Hyeong</au><au>Kim, Jin‐Woo</au><au>Kim, Jiyool</au><au>Lee, Bok‐Soo</au><au>Kim, Ye Ji</au><au>Park, Seongchan</au><au>Khaleel, Zinah Hilal</au><au>Sa, Deok Hyang</au><au>Lee, Eui‐Chul</au><au>Lee, Jaecheol</au><au>Ham, Jungyeob</au><au>Kim, Jin‐Chul</au><au>Kim, Yong Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peptide‐Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis‐Like Inflammation</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>13</volume><issue>15</issue><spage>e2303480</spage><epage>n/a</epage><pages>e2303480-n/a</pages><issn>2192-2640</issn><issn>2192-2659</issn><eissn>2192-2659</eissn><abstract>Peptide‐drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, physicochemical criteria based on cell‐penetrating peptides are employed to design transcellular peptides derived from an antimicrobial peptides library. Among the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, it is found that 6‐Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti‐inflammatory PDC. The transcellular PDC (SDT7‐conjugated with PAR, named TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular PDCs (TDCs) as a promising approach for the treatment of inflammatory skin disorders.
Transcellular peptides (SDTs) derived from antimicrobial peptides are designed based on cell‐penetrating peptides for efficient delivery through the skin barrier. 6‐Paradol (PAR) is conjugated with SDT7 to treat psoriatic skin inflammation by inhibiting phosphodiesterase 4. The transcellular peptide‐drug conjugate (TM5) exhibits superior efficacy in psoriasis mouse models suggesting a promise for treating inflammatory skin disorders.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38421096</pmid><doi>10.1002/adhm.202303480</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9106-3298</orcidid></addata></record> |
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| source | Wiley-Blackwell Journals |
| subjects | Animal models Antimicrobial peptides anti‐inflammation Bioavailability Cell permeability Conjugates Drug delivery Drug delivery systems Drug development ginger‐driven compounds Peptides peptide‐drug conjugates Permeability Pharmacology Phosphodiesterase IV Psoriasis skin barrier Skin diseases transcellular peptide |
| title | Peptide‐Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis‐Like Inflammation |
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