View in EDS

The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides.

Saved in:
Bibliographic Details
Title: The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides.
Authors: Szwej, Emilia1, Devocelle, Marc2, Kenny, Shane1, Guzik, Maciej1, O’Connor, Stephen1, Nikodinovic-Runic, Jasmina3, Radivojevic, Jelena3,4, Maslak, Veselin4, Byrne, Annete T.1,5, Gallagher, William M.1, Zulian, Qun Ren6, Zinn, Manfred6, O’Connor, Kevin E.1 kevin.oconnor@ucd.ie
Source: Journal of Biotechnology. Jun2015, Vol. 204, p7-12. 6p.
Subjects: Antineoplastic agents, Alkanoic acids, Bacterial conjugation, Peptides, Biopolymers, Chain length (Chemistry)
Abstract: Conjugation of DP18L peptide with ( R )-3-hydroxydecanoic acid, derived from the biopolymer polyhydroxyalkanoate, enhances its anti-cancer activity (O’Connor et al., 2013. Biomaterials 34, 2710–2718). However, it is unknown if other ( R )-3-hydroxyalkanoic acids (R3HAs) can enhance peptide activity, if chain length affects enhancement, and what effect R3HAs have on peptide structure. Here we show that the degree of enhancement of peptide (DP18L) anti-cancer activity by R3HAs is carbon chain length dependent. In all but one example the R3HA conjugated peptides were more active against cancer cells than the unconjugated peptides. However, R3HAs with 9 and 10 carbons were most effective at improving DP18L activity. DP18L peptide variant DP17L, missing a hydrophobic amino acid (leucine residue 4) exhibited lower efficacy against MiaPaCa cells. Circular dichroism analysis showed DP17L had a lower alpha helix content and the conjugation of any R3HA (( R )-3-hydroxyhexanoic acid to ( R )-3-hydroxydodecanoic acid) to DP17L returned the helix content back to levels of DP18L. However ( R )-3-hydroxyhexanoic did not enhance the anti-cancer activity of DP17L and at least 7 carbons were needed in the R3HA to enhance activity of D17L. DP17L needs a longer chain R3HA to achieve the same activity as DP18L conjugated to an R3HA. As a first step to assess the synthetic potential of polyhydroxyalkanoate derived R3HAs, ( R )-3-hydroxydecanoic acid was synthetically converted to (±)3-chlorodecanoic acid, which when conjugated to DP18L improved its antiproliferative activity against MiaPaCa cells. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biotechnology 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
FullText Text:
  Availability: 0
Header DbId: egs
DbLabel: Engineering Source
An: 102621992
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Szwej%2C+Emilia%22">Szwej, Emilia</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Devocelle%2C+Marc%22">Devocelle, Marc</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Kenny%2C+Shane%22">Kenny, Shane</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Guzik%2C+Maciej%22">Guzik, Maciej</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22O’Connor%2C+Stephen%22">O’Connor, Stephen</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Nikodinovic-Runic%2C+Jasmina%22">Nikodinovic-Runic, Jasmina</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Radivojevic%2C+Jelena%22">Radivojevic, Jelena</searchLink><relatesTo>3,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Maslak%2C+Veselin%22">Maslak, Veselin</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Byrne%2C+Annete+T%2E%22">Byrne, Annete T.</searchLink><relatesTo>1,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Gallagher%2C+William+M%2E%22">Gallagher, William M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zulian%2C+Qun+Ren%22">Zulian, Qun Ren</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Zinn%2C+Manfred%22">Zinn, Manfred</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22O’Connor%2C+Kevin+E%2E%22">O’Connor, Kevin E.</searchLink><relatesTo>1</relatesTo><i> kevin.oconnor@ucd.ie</i>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biotechnology%22">Journal of Biotechnology</searchLink>. Jun2015, Vol. 204, p7-12. 6p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Antineoplastic+agents%22">Antineoplastic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Alkanoic+acids%22">Alkanoic acids</searchLink><br /><searchLink fieldCode="DE" term="%22Bacterial+conjugation%22">Bacterial conjugation</searchLink><br /><searchLink fieldCode="DE" term="%22Peptides%22">Peptides</searchLink><br /><searchLink fieldCode="DE" term="%22Biopolymers%22">Biopolymers</searchLink><br /><searchLink fieldCode="DE" term="%22Chain+length+%28Chemistry%29%22">Chain length (Chemistry)</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Conjugation of DP18L peptide with ( R )-3-hydroxydecanoic acid, derived from the biopolymer polyhydroxyalkanoate, enhances its anti-cancer activity (O’Connor et al., 2013. Biomaterials 34, 2710–2718). However, it is unknown if other ( R )-3-hydroxyalkanoic acids (R3HAs) can enhance peptide activity, if chain length affects enhancement, and what effect R3HAs have on peptide structure. Here we show that the degree of enhancement of peptide (DP18L) anti-cancer activity by R3HAs is carbon chain length dependent. In all but one example the R3HA conjugated peptides were more active against cancer cells than the unconjugated peptides. However, R3HAs with 9 and 10 carbons were most effective at improving DP18L activity. DP18L peptide variant DP17L, missing a hydrophobic amino acid (leucine residue 4) exhibited lower efficacy against MiaPaCa cells. Circular dichroism analysis showed DP17L had a lower alpha helix content and the conjugation of any R3HA (( R )-3-hydroxyhexanoic acid to ( R )-3-hydroxydodecanoic acid) to DP17L returned the helix content back to levels of DP18L. However ( R )-3-hydroxyhexanoic did not enhance the anti-cancer activity of DP17L and at least 7 carbons were needed in the R3HA to enhance activity of D17L. DP17L needs a longer chain R3HA to achieve the same activity as DP18L conjugated to an R3HA. As a first step to assess the synthetic potential of polyhydroxyalkanoate derived R3HAs, ( R )-3-hydroxydecanoic acid was synthetically converted to (±)3-chlorodecanoic acid, which when conjugated to DP18L improved its antiproliferative activity against MiaPaCa cells. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biotechnology 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=102621992
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.jbiotec.2015.02.036
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 6
        StartPage: 7
    Subjects:
      – SubjectFull: Antineoplastic agents
        Type: general
      – SubjectFull: Alkanoic acids
        Type: general
      – SubjectFull: Bacterial conjugation
        Type: general
      – SubjectFull: Peptides
        Type: general
      – SubjectFull: Biopolymers
        Type: general
      – SubjectFull: Chain length (Chemistry)
        Type: general
    Titles:
      – TitleFull: The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Szwej, Emilia
      – PersonEntity:
          Name:
            NameFull: Devocelle, Marc
      – PersonEntity:
          Name:
            NameFull: Kenny, Shane
      – PersonEntity:
          Name:
            NameFull: Guzik, Maciej
      – PersonEntity:
          Name:
            NameFull: O’Connor, Stephen
      – PersonEntity:
          Name:
            NameFull: Nikodinovic-Runic, Jasmina
      – PersonEntity:
          Name:
            NameFull: Radivojevic, Jelena
      – PersonEntity:
          Name:
            NameFull: Maslak, Veselin
      – PersonEntity:
          Name:
            NameFull: Byrne, Annete T.
      – PersonEntity:
          Name:
            NameFull: Gallagher, William M.
      – PersonEntity:
          Name:
            NameFull: Zulian, Qun Ren
      – PersonEntity:
          Name:
            NameFull: Zinn, Manfred
      – PersonEntity:
          Name:
            NameFull: O’Connor, Kevin E.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 20
              M: 06
              Text: Jun2015
              Type: published
              Y: 2015
          Identifiers:
            – Type: issn-print
              Value: 01681656
          Numbering:
            – Type: volume
              Value: 204
          Titles:
            – TitleFull: Journal of Biotechnology
              Type: main
ResultId 1