Synthesis and conformational studies of poly(l-lysine) based branched polypeptides with Ser and Glu/Leu in the side chains

Abstract

In a new group of polypeptides, the branches were composed of dl-Ala oligopeptide, l-serine and l-leucine or l-glutamic acid residues. The synthesis of eight different side-chain combinations is described. In the first group, Ser was attached directly to the ε-amino groups of polylysine, and Leu or Glu was situated at the side chain end (poly[Lys(Xi–dl-Alam–Serj)]). Alternatively, Leu or Glu was positioned next to the polylysine backbone (poly[Lys(Serj–dl-Alam–Xi)], where X=l-Leu or l-Glu and m∼3–6, i≤1 and j≤1). The second group of polymers was synthesised by grafting oligo(dl-alanine) chains to the ϵ-amino groups of polylysine, followed by coupling of Ser and Leu or Glu consecutively to the chain ends, however, in a different order, resulting in the polymers (poly[Lys(Xi–Serj–dl-Alam)] and poly[Lys(Serj–Xi–dl-Alam)], where X=l-Leu or l-Glu and m∼3–6, i≤1 and j≤1). The effect of amino-acid composition and sequence of side chains in branched polypeptides on solution conformation was studied by CD spectroscopy. CD spectra recorded in aqueous solutions of various pH (2–11) and ionic strengths (0.02–2.0 M NaCl) suggest that leucine- and serine-containing polypeptides have more ordered (α-helical) structure than the polymers with glutamic acid and serine residues in the same position. The influence of serine residues on ordered structure (helical or β-sheet) formation depends on its position in the side chain as well as on the nature of amino acid X (Leu or Glu). The incorporation of Ser into the branches resulted in polypeptides possessing prolonged shelf stability and high water-solubility. No toxic effect of this new class of polymers was observed on mouse spleen cells, even after 4 h of incubation.