Conjugation of HS-oligopeptides with polymeric branched chain polypeptides containing multiple amino groups

I. Nagy, Andrea Dancs, György Kóczán, G. Mező, F. Hudecz

Research output: Contribution to journalArticle

Abstract

For the preparation of bioconjugates containing polymeric polypeptides with well-defined structure and composition, we systematically studied 3-(2- pyridyldithio)propionic acid N-hydroxy-succinimide ester (SPDP). SPDP as amino- and thiol-reactive heterobifunctional coupling agent is mainly used for protein-based conjugates, and very little data are available on its application for the modification of polymers. In this communication, we describe the effect of polymer/oligopeptide structure and of the reaction condition on the incorporation of oligopeptides with free thiol group (CAVKDEL, CTGRGDSP) into polymeric polypeptides possessing multiple amino groups. For these studies, linear poly[L-lysine] with free ε-amino groups and its XAK-type branched polypeptide derivatives {poly[Lys(X(i)-DL-Ala(m)] (i < 1, m ~ 3, XAK)} either with polycationic character {X = ∅ (AK), X = Ser (SAK)} or with amphoteric nature {X = Glu (EAK)} were utilized. First, the polymers were modified with SPDP under various conditions, and the degree of substitution was determined. We found that the efficacy of the nucleophilic substitution of NH2 groups with SPDP depended not only on the pH and the concentration of the coupling reagent but also on the polymer composition, mainly on the pKα of the branch-terminal amino group of the polymers. SPDP-modified polymeric polypeptides were reacted with the HS- oligopeptides, and the effects of polymer/oligopeptide structure as well as the reaction conditions (pH, peptide/(SSP)polymer molar ratio) on the composition of the product were evaluated. The results suggest that acidic pH is more favorable for the thiol-disulphide exchange, and the side chain composition of the polymers had a pronounced effect while the chemical structure of oligopeptides had only moderate influence on the average degree of substitution.

Original languageEnglish
Pages (from-to)139-154
Number of pages16
JournalJournal of Bioactive and Compatible Polymers
Volume15
Issue number2
DOIs
Publication statusPublished - Jan 1 2000

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ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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