Carrier design: synthesis and conformational studies of poly(l-lysine) based brancheid polypeptides with hydroxyl groups in the side chains

G. Mezö, J. Kajtâr, I. Nagy, M. Szekerke, F. Hudecz

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In the present study the development of a new series of branched polypeptides that contain hydroxyl groups in side chains is reported. Serine or threonine were attached by 1hydroxy-benzotriazole catalyzed active ester method to the N-terminals of oligo(DL-alanine) chains grafted to a polylysine backbone resulted in poly[Lys-(Seri-DL-Alam)] (SAK) andpoly[Lys-(ThrrDL-Alam)] (TAK). Serwas coupled also directly to the e-amino groups of polylysine followed by polymerization of N-carboxy-DL-alanine anhydride resulting oligo(DL-Ala) chain terminals. In this way a reverse sequence was built up in the side chain corresponding to the poly[Lys-(DL-Alam-Ser,)] (ASK). The number of hydroxyl groups in the polymer was increased by the synthesis of a branched polypeptide with oligo(DL-serine) branches instead ofoligo(DLalanine) ones-poly[Lys-(DL-Serm)] (SK). Classification of solution conformations of branched polypeptides was carried out by CD spectroscopy performed in water solution of various pH values and ionic strengths. Incorporation of single Ser residues in poly[Lys-(X-,)]type polypeptides markedly promotes the formation of ordered structure without resulting precipitation even in high salt concentration. The presence of branches with multiple DL-Ser residues resulted in a slightly decreased ability of the polypeptide backbone to adopt an ordered conformation. Comparison of the CD properties of the SAK-ASK pair demonstrates that these compounds are similar, showing an increased tendency to form an ordered spatial arrangement in solution at elevated pH or ionic strength; however, differences in their CD spectra suggest that SAK has higher capability to form regular conformation under comparable conditions. The replacement of Ser by the Thr residue in poly[Lys-(Xi-DL-Alam)] induced a confonnational transition and TAK exhibited a more helical structure. These results might indicate that not only hydrophobia or ionic attraction, but also H-bond interaction, can play a role in the formation and/or stabilization of ordered conformation of branched polypeptides. Findings with the hydroxyl group containing polymers reported in this paper can also explain their prolonged shelf stability and high water solubility.

Original languageEnglish
Pages (from-to)719-730
Number of pages12
JournalBiopolymers - Nucleic Acid Sciences Section
Issue number6
Publication statusPublished - Jan 1 1997



  • Branched polypeptides
  • Carrier design
  • Hydroxyl groups
  • Poly(l-lysine)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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