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Protease-induced release of functional peptides from bioplexes

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Title: Protease-induced release of functional peptides from bioplexes
Authors: Svahn, Mathias G.1 mathias.svahn@crc.ki.se, Salih, Gaza1, Oscar Simonson, E.1, Edvard Smith, C.I.1 edvard.smith@crc.ki.se, Brandén, Lars J.1,2
Source: Journal of Controlled Release. Jul2004, Vol. 98 Issue 1, p169-177. 9p.
Subjects: Hydrolases, Proteolytic enzymes, Peptides, Proteins
Abstract: Linking peptide functions directly to nucleic acids can be used to improve transfection. We have previously demonstrated this by sequence-specific hybridization of a bifunctional peptide nucleic acid (PNA) consisting of a nucleic acid binding moiety conjugated to a peptide. The resulting biological complex of PNA/DNA is called a Bioplex. The bifunctional PNA is continuously synthesized with one or more functional entities. For certain applications, it might be preferable to eliminate a functional entity after it has served its purpose. We have addressed this issue by adding a specific protease cleavage site to the construct. In this first approach, cathepsin L was used to cleave a linker sequence including a cathepsin L site: afrsaaq, thereby releasing the tri-peptide Arg–Gly–Asp (RGD) from the PNA anchor. In vitro and in vivo experiments showed an efficient cleavage of the peptide. Moreover, bifunctional PNA constructs were shown to retain activity of the second entity following removal of the first function. Since cathepsin L is ubiquitously expressed in eukaryotic cells and becomes active as the endosomal pH drops, inclusion of cathepsin sites makes it possible to remove functional entities in late endosomes/early lysosomes. [Copyright &y& Elsevier]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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PubType: Academic Journal
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  Data: Protease-induced release of functional peptides from bioplexes
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  Data: <searchLink fieldCode="AR" term="%22Svahn%2C+Mathias+G%2E%22">Svahn, Mathias G.</searchLink><relatesTo>1</relatesTo><i> mathias.svahn@crc.ki.se</i><br /><searchLink fieldCode="AR" term="%22Salih%2C+Gaza%22">Salih, Gaza</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Oscar+Simonson%2C+E%2E%22">Oscar Simonson, E.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Edvard+Smith%2C+C%2EI%2E%22">Edvard Smith, C.I.</searchLink><relatesTo>1</relatesTo><i> edvard.smith@crc.ki.se</i><br /><searchLink fieldCode="AR" term="%22Brandén%2C+Lars+J%2E%22">Brandén, Lars J.</searchLink><relatesTo>1,2</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. Jul2004, Vol. 98 Issue 1, p169-177. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Hydrolases%22">Hydrolases</searchLink><br /><searchLink fieldCode="DE" term="%22Proteolytic+enzymes%22">Proteolytic enzymes</searchLink><br /><searchLink fieldCode="DE" term="%22Peptides%22">Peptides</searchLink><br /><searchLink fieldCode="DE" term="%22Proteins%22">Proteins</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Linking peptide functions directly to nucleic acids can be used to improve transfection. We have previously demonstrated this by sequence-specific hybridization of a bifunctional peptide nucleic acid (PNA) consisting of a nucleic acid binding moiety conjugated to a peptide. The resulting biological complex of PNA/DNA is called a Bioplex. The bifunctional PNA is continuously synthesized with one or more functional entities. For certain applications, it might be preferable to eliminate a functional entity after it has served its purpose. We have addressed this issue by adding a specific protease cleavage site to the construct. In this first approach, cathepsin L was used to cleave a linker sequence including a cathepsin L site: afrsaaq, thereby releasing the tri-peptide Arg–Gly–Asp (RGD) from the PNA anchor. In vitro and in vivo experiments showed an efficient cleavage of the peptide. Moreover, bifunctional PNA constructs were shown to retain activity of the second entity following removal of the first function. Since cathepsin L is ubiquitously expressed in eukaryotic cells and becomes active as the endosomal pH drops, inclusion of cathepsin sites makes it possible to remove functional entities in late endosomes/early lysosomes. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=13702915
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        Value: 10.1016/j.jconrel.2004.04.012
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      – Code: eng
        Text: English
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        Type: general
      – SubjectFull: Proteolytic enzymes
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      – SubjectFull: Peptides
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      – SubjectFull: Proteins
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              Text: Jul2004
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