The remarkable stability of chimeric, sialic acid-derived α/δ-peptides in human blood plasma

Jonel P. Saludes, Arutselvan Natarajan, Sally J. Denardo, Jacquelyn Gervay-Hague

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Peptides are labile toward proteolytic enzymes, and structural modifications are often required to prolong their metabolic half-life and increase resistance. One modification is the incorporation of α-amino acids into the peptide to deter recognition by hydrolytic enzymes. We previously reported the synthesis of chimeric α\Δ-peptides from glutamic acids (Glu) and the sialic acid derivative Neu2en. Conformational analyses revealed these constructs adopt secondary structures in water and may serve as conformational surrogates of polysialic acid. Polysialic acid is a tumor-associated polysaccharide and is correlated with cancer metastasis. Soluble polysialic acid is rapidly cleared from the blood limiting its potential for vaccine development. One motivation in developing structural surrogates of polysialic acid was to create constructs with increased bioavailability. Here, we report plasma stability profiles of Glu/Neu2en α/Δ-peptides. DOTA was conjugated at the peptide N-termini by solid phase peptide synthesis, radiolabeled with 111In, incubated in human blood plasma at 37 °C, and their degradation patterns monitored by cellulose acetate electrophoresis and radioactivity counting. Results indicate that these peptides exhibit a long half-life that is two- to three-orders of magnitude higher than natural α-peptides. These findings provide a viable platform for the synthesis of plasma stable, sialic acid-derived peptides that may find pharmaceutical application.

Original languageEnglish (US)
Pages (from-to)455-460
Number of pages6
JournalChemical Biology and Drug Design
Volume75
Issue number5
DOIs
StatePublished - May 2010

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N-Acetylneuraminic Acid
Blood
Plasmas
Peptides
Half-Life
Glutamates
Cellulose Acetate Electrophoresis
Solid-Phase Synthesis Techniques
Plasma stability
Radioactivity
Biological Availability
Electrophoresis
Polysaccharides
Neoplasms
Peptide Hydrolases
Vaccines
Tumors
Neoplasm Metastasis
Amino Acids
Derivatives

Keywords

  • Cellulose acetate electrophoresis
  • Chimeric α\δ-peptides
  • DOTA
  • Glutamic acid
  • Neu2en
  • Plasma stability
  • Radiochelate
  • Sialic acid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

The remarkable stability of chimeric, sialic acid-derived α/δ-peptides in human blood plasma. / Saludes, Jonel P.; Natarajan, Arutselvan; Denardo, Sally J.; Gervay-Hague, Jacquelyn.

In: Chemical Biology and Drug Design, Vol. 75, No. 5, 05.2010, p. 455-460.

Research output: Contribution to journalArticle

Saludes, Jonel P. ; Natarajan, Arutselvan ; Denardo, Sally J. ; Gervay-Hague, Jacquelyn. / The remarkable stability of chimeric, sialic acid-derived α/δ-peptides in human blood plasma. In: Chemical Biology and Drug Design. 2010 ; Vol. 75, No. 5. pp. 455-460.
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