Salt bridge induced changes in the secondary structure of ionic polypeptides

Area of Science:

• Biochemistry
• Polymer Science
• Materials Science

Background:

• Poly(L-glutamate) [poly(Glu)] and poly(L-aspartate) [poly(Asp)] are carboxylate-containing homopolypeptides.
• Poly(L-lysine) [poly(Lys)] is a positively charged polypeptide.
• Understanding polypeptide interactions is crucial for biomaterials and drug delivery.

Purpose of the Study:

• To investigate the different ordered structures formed by poly(Glu) and poly(Asp) in the presence of poly(Lys).
• To elucidate the role of divalent cations (Ca2+ and Mg2+) in the stability and dissolution of these polypeptide aggregates.

Main Methods:

• Mixing poly(Glu) and poly(Lys) in aqueous solution at neutral pH.
• Mixing poly(Asp) and poly(Lys) under identical conditions.
• Infrared (IR) spectroscopy to analyze secondary structures.
• Addition of Ca2+ and Mg2+ solutions to observe dissolution and reaggregation.

Main Results:

• Poly(Glu)/poly(Lys) mixtures formed a gel-like precipitate with intermolecular antiparallel beta-strands (IR bands at 1684 and 1612 cm-1).
• Poly(Asp)/poly(Lys) mixtures formed a fine precipitate lacking discrete secondary structure.
• Ca2+ or Mg2+ dissolved the poly(Glu)/poly(Lys) gel by disrupting the hydrogen-bonded network.
• Reaggregation of poly(Glu)/poly(Lys) occurred upon heating with Ca2+ but not Mg2+.

Conclusions:

• Salt bridges play a critical role in forming strong hydrogen bonds between polypeptide backbone amide groups.
• The secondary structure and aggregation behavior of poly(Glu) and poly(Asp) differ significantly in the presence of poly(Lys).
• Divalent cations influence the stability and structural transitions of these polypeptide complexes.