Spiegelmeric 4R/S-hydroxy/amino-L/D-prolyl collagen peptides: conformation and morphology of self-assembled structures

Abstract

The primary structure of collagen, the major protein in connective tissue of mammals, comprises of repeating triads [((L)Pro-(L)Hyp-Gly)(n), P1, (L)Hyp being 4R-hydroxy-lProline)] in a single strand that adopts left-handed polyproline II type helix. Three such single stranded helices wind around each another and held together by interchain H-bonds to form right-handed triple helix. This manuscript reports on collagen derived from its mirror image triad [((D)Pro-(D)Hyp-Gly)(n), P2, (D)Hyp being 4S-hydroxy-(D)Proline) and its 4-amino analogue ((D)Pro-(D)Amp-Gly)(n) P4, (D)Amp being 4S-amino-(D)Proline that form corresponding spiegelmeric triplexes. The amino L-collagen peptide ((L)Pro-(L)Amp-Gly)(n) P3 and its D-analogue P4 show higher thermal stabilities compared to 4-hydroxy-lProline collagen peptides P1 and P2. The enantiomeric peptide pairs show mirror image CD profiles and identical thermal stability, with ionizable 4-amino group in P3 and P4 imparting pH dependent triplex stability. Upon cold mixing of the L- and D-collagen peptides, different morphological nanostructures arise from inter triplex peptide association. When the peptides are hot mixed (annealed), the inter peptide association occurs via interaction of single stranded peptide chains of opposite handedness leading to networked gel formation in P1 and P2, while the charged peptides P3 and P4 show more ordered nanofibers, different from the enantiomerically pure peptides. The nanocomposites of such chiral hybrid peptides may have not only interesting physicomorphology, but also biological properties that need exploration.