Collagen-like triple helix formation of synthetic (Pro-Pro-Gly)10 analogues: (4(S)-hydroxyprolyl-4(R)-hydroxyprolyl-Gly)10, (4(R)-hydroxyprolyl-4(R)-hydroxyprolyl-Gly)10 and (4(S)-fluoroprolyl-4(R)-fluoroprolyl-Gly)10.
For the rational design of a stable collagen triple helix according to the conventional rule that the pyrrolidine puckerings of Pro, 4-hydroxyproline (Hyp) and 4-fluoroproline (fPro) should be down at the X-position and up at the Y-position in the X-Y-Gly repeated sequence for enhancing the triple helix propensities of collagen model peptides, a series of peptides were prepared in which X- and Y-positions were altogether occupied by Hyp(R), Hyp(S), fPro(R) or fPro(S). Contrary to our presumption that inducing the X-Y residues to adopt a down-up conformation would result in an increase in the thermal stability of peptides, the triple helices of (Hyp(S)-Hyp(R)-Gly)(10) and (fPro(S)-fPro(R)-Gly)(10) were less stable than those of (Pro-Hyp(R)-Gly)(10) and (Pro-fPro(R)-Gly)(10), respectively. As reported by Bächinger's and Zagari's groups, (Hyp(R)-Hyp(R)-Gly)(10) which could have an up-up conformation unfavorable for the triple helix, formed a triple helix that has a high thermal stability close to that of (Pro-Hyp(R)-Gly)(10). These results clearly show that the empirical rule based on the conformational preference of pyrrolidine ring at each of X and Y residues should not be regarded as still valid, at least for predicting the stability of collagen models in which both X and Y residues have electronegative groups at the 4-position.
Doi
Masamitsu
M
Department of Materials Science, Wakayama National College of Technology, Wakayama 644-0023, Japan.
Nishi
Yoshinori
Y
Uchiyama
Susumu
S
Nishiuchi
Yuji
Y
Nishio
Hideki
H
Nakazawa
Takashi
T
Ohkubo
Tadayasu
T
Kobayashi
Yuji
Y
D003094:Collagen / Q000031:analogs & derivatives* / Q000737:chemistry*; D006909:Hydroxyproline / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D009842:Oligopeptides; C044555:prolyl-prolyl-glycine; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline