title: 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 epsilon-amino groups of polylysine, and Leu or Glu was situated at the side chain end (poly[Lys(X(i)-DL-Ala(m)-Ser(j))]). Alternatively, Leu or Glu was positioned next to the polylysine backbone (poly[Lys(Ser(j)-DL-Ala(m)-X(i))], where X=L-Leu or L-Glu and m approximately 3-6, i</=1 and j</=1). The second group of polymers was synthesised by grafting oligo(DL-alanine) chains to the epsilon-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(X(i)-Ser(j)-DL-Ala(m))] and poly[Lys(Ser(j)-X(i)-DL-Ala(m))], where X=L-Leu or L-Glu and m approximately 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 (alpha-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 beta-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.
authors.affiliation: Research Group of Peptide Chemistry, Hungarian Academy of Sciences, H-1518, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Mezö
authors.forename: J
authors.initials: J
authors.lastname: Reményi
authors.forename: J
authors.initials: J
authors.lastname: Kajtár
authors.forename: K
authors.initials: K
authors.lastname: Barna
authors.forename: D
authors.initials: D
authors.lastname: Gaál
authors.forename: F
authors.initials: F
authors.lastname: Hudecz
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry*; D007930:Leucine / Q000737:chemistry*; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012694:Serine / Q000737:chemistry*; D012996:Solutions; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D009842:Oligopeptides; D012996:Solutions; D011107:Polylysine; D018698:Glutamic Acid; D012694:Serine; D007930:Leucine