Collagen mimics
Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly) n ,where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.
1. A composition of matter comprising a triple helix of collagen mimic molecules in which each of the molecules in the helix comprises tripeptides of the formula:
(flp-Yaa-Gly)n,
where Yaa is a (2S,4S)-4-alkylproline or a (2S,4S)-4-thioproline,
where flp is (2S,4S)-4-fluoroproline, and
n is a positive integer.
2. A composition of matter as claimed in claim 1 wherein n is at least 3.
3. A composition of matter comprising a triple helix of collagen mimic molecules in which each of the molecules in the helix comprises tripeptides of the formula:
(Xaa-Flp-Gly)n,
where Xaa is selected from the group consisting of (2S,4R)-4-alkylproline or a (2S,4R)-4-thioproline,
where Flp is (2S,4R)-4-fluoroproline, and
n is a positive integer.
4. The peptide of claim 3 , wherein n is at least 3.
5. The composition of claim 1 , wherein the (2S,4S)-4-alkylproline is selected from the group consisting of 4-methylproline, 4-ethylproline, 4-propylproline, 4-isopropylproline, or a longer alkyl proline, and wherein an electronegative atom including N, O, F, Cl, or Br is not installed directly on C4 of the proline ring.
6. The composition of claim 1 , wherein Yaa is (2S,4S)-4-alkyl proline wherein the 4-alkyl is 4-methyl, 4-ethyl, 4-propyl or 4-isopropyl, or (2S,4S)-4-thioproline wherein the 4-thio is -SH, and wherein an electronegative atom including N, O, F, Cl, or Br is not installed directly on C4 of the proline ring.
7. The composition of claim 6 , wherein the Yaa is the (2S,4S)-4-alkyl proline wherein the 4-alkyl is 4-methyl, 4-ethyl, 4-propyl or 4-isopropyl.
8. The composition of claim 1 , wherein the tripeptide is selected from the group consisting of (flp-Mep-Gly) n , and (flp-Thp-Gly) n , wherein n is a positive integer that is at least 3.
9. The composition of claim 3 , wherein the (2S,4R)-4-alkylproline is selected from the group consisting of 4-methylproline, 4-ethylproline, 4-propylproline, 4-isopropylproline, or a longer alkyl proline, and wherein an electronegative atom including N, O, F, Cl, or Br is not installed directly on C4 of the proline ring.
10. The composition of claim 3 , wherein Xaa is (2S,4R)-4-alkylproline wherein the 4-alkyl is 4-methyl, 4-ethyl, 4-propyl or 4-isopropyl, or (2S,4R)-4-thioproline wherein the 4-thio is —SH, and wherein an electronegative atom including N, O, F, Cl, or Br is not installed directly on C4 of the proline ring.
11. The composition of claim 10 , wherein the Xaa is the (2S,4R)-4-alkylproline wherein the 4-alkyl is 4-methyl, 4-ethyl, 4-propyl or 4-isopropyl.
12. The composition of claim 3 , wherein the tripeptide is selected from the group consisting of (mep-Flp-Gly) n , and (thp-Flp-Gly) n , wherein n is a positive integer that is at least 3.