Synthesis and stabilization of amino and carboxy terminal constrained collagenous peptides

Abstract

Short collagenous peptides cross‐linked at their amino and carboxy termini with Lys‐Lys‐dimer template(s) were synthesized, and the effect of the cross‐linking on their stabilities was investigated by thermal denaturation experiments. Two chemoselective ligations were used for the construction of the amino and the carboxy cross‐linked peptides. The thermal transition temperature (Tm) and the standard free energies (ΔG°) of the cross‐linked collagenous peptides increased, and the thermal stabilization effect corresponded to an elongation by two units of the Gly‐Pro‐Hyp triad. The van't Hoff enthalpy (ΔH°) and the entropy (ΔS°) values of the cross‐linked peptides increased with chain elongation, although the increments were smaller than those of the linear peptides. When the same chain lengths were compared, the ΔH° was increased and the ΔS° was nearly the same or increased by the cross‐linking. These results suggest that the cross‐linking of the collagenous peptides with the Lys‐Lys‐dimer template(s) for stabilization contributes to the enthalpic effect, rather than the entropic effect.

Metal ion‐assembled micro‐collagen heterotrimers

“…The melting temperatures are modest, and similar to those reported by other groups for similar length (POG) n sequences. 4b,4m,5,22 Uncertainties in the oligomerization states preclude any determination of thermodynamic folding parameters.…”

Synthesis and biological applications of collagen-model triple-helical peptides

“…Collagenous linear peptides of the sequence Cys-Gly-(Gly-Pro-Hyp) n -Lys(Ser)-NH 2 ( n = 3–10) ( 1 ) were then synthesized using Fmoc chemistry. 76 The trivalent linker, tris-bromoacetylated Lys-Lys dimer 2 , was prepared on MBHA resin. The tris-aminooxyacetylated branch-peptide 3 was synthesized by a similar method using Boc-aminooxyacetic acid instead of bromoacetic acid.…”

The Thermodynamics and Kinetics of Collagen Folding

“…Other covalent linkers include Kemp triacid [40], a modified dilysine system [41], the sequence found at the C-terminal end of type III collagen Gly-Pro-Cys-Cys-Gly [42][43][44][45][46], and tris(2-aminoethyl)amine with succinic acid spacers [47]. Peptides with covalent crosslinks at both ends were also synthesized [48]. The noncovalent obligatory trimer foldon [46], peptide amphiphiles [49][50][51], and the iron (II) complex of bipyridine [52] have also been used to study trimeric peptides.…”