Stabilization of triple‐helical structures of collagen peptides containing a Hyp‐Thr‐Gly, Hyp‐Val‐Gly, or Hyp‐Ser‐Gly sequence

The single‐crystal structures of three collagen‐like host–guest peptides, (Pro‐Pro‐Gly) 4 ‐Hyp‐Yaa‐Gly‐(Pro‐Pro‐Gly) 4 [Yaa = Thr, Val, Ser; Hyp = (4 R )‐4‐hydroxyproline] were analyzed at atomic resolution. These peptides adopted a 7/2‐helical structure similar to that of the (Pro‐Pro‐Gly) 9 peptide. The stability of these triple helices showed a similar tendency to that observed in Ac‐(Gly‐Hyp‐Yaa) 10 ‐NH 2 (Yaa = Thr, Val, Ser) peptides. On the basis of their detailed structures, the differences in the triple‐helical stabilities of the peptides containing a Hyp‐Thr‐Gly, Hyp‐Val‐Gly, or Hyp‐Ser‐Gly sequence were explained in terms of van der Waals interactions and dipole–dipole interaction between the Hyp residue in the X position and the Yaa residue in the Y position involved in the Hyp(X):Yaa(Y) stacking pair. This idea also explains the inability of Ac‐(Gly‐Hyp‐alloThr) 10 ‐NH 2 and Ac‐(Gly‐Hyp‐Ala) 10 ‐NH 2 peptides to form triple helices. In the Hyp(X):Thr(Y), Hyp(X):Val(Y), and Hyp(X):Ser(Y) stacking pairs, the proline ring of the Hyp residues adopts an up‐puckering conformation, in agreement with the residual preference of Hyp, but in disagreement with the positional preference of X in the Gly‐Xaa‐Yaa sequence. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 628–640, 2011.