Tricine as a convenient scaffold for the synthesis of C-terminally branched collagen-model peptides

Abstract

A novel and convenient method for the synthesis of -terminally branched collagen-model peptides has been achieved using tricine (-[tris(hydroxymethyl)methyl]glycine) as a branching scaffold and 1,2-diaminoethane or 1,4-diaminobutane as a linker. The peptide sequence was incorporated directly onto the linker and scaffold during solid-phase synthesis without additional manipulations. The resulting branched triple-helical peptides exhibited comparable thermal stabilities to the parent, unbranched sequence, and served as substrates for matrix metalloproteinase-1 (MMP-1). The tricine-based branch reported herein represents the simplest synthetic scaffold for the convenient synthesis of covalently linked homomeric collagen-model triple-helical peptides.

Recent Advances in Collagen Mimetic Peptide Structure and Design

“…91 Both branching strategies work well for homotrimer synthesis however tricine with either of the tested linkers showed a lower melting temperature than the unbranched CMP, while dilysine branching had an increase in 5 °C above the unbranched CMP. 91 However, this new tricine method does not require additional protecting groups while the dilysine branching strategy requires two orthogonally protected Lys residues. 91 Another cross-linking strategy takes advantage of proline analogs, 4-amino-oxyproline (Aop) and 4-oxoacetamidoproline (Alp), for both their preorganization to stabilize the triple helix and ability to undergo an oxime ligation (Figure 8E).…”

“…91 However, this new tricine method does not require additional protecting groups while the dilysine branching strategy requires two orthogonally protected Lys residues. 91 Another cross-linking strategy takes advantage of proline analogs, 4-amino-oxyproline (Aop) and 4-oxoacetamidoproline (Alp), for both their preorganization to stabilize the triple helix and ability to undergo an oxime ligation (Figure 8E). 92 First, the stereochemistry for each amino acid was selected, with both containing an electron-withdrawing group like hydroxyproline, 4R leads to C γ -exo conformation, more favorable in the Yaa position, and 4S leads to a C γ -endo conformation more 91 (E) Oxime ligation cross-linking between 4S-aminooxyproline (Aop) and 4R-oxoacetamidoproline (Alp).…”

“…91 Another cross-linking strategy takes advantage of proline analogs, 4-amino-oxyproline (Aop) and 4-oxoacetamidoproline (Alp), for both their preorganization to stabilize the triple helix and ability to undergo an oxime ligation (Figure 8E). 92 First, the stereochemistry for each amino acid was selected, with both containing an electron-withdrawing group like hydroxyproline, 4R leads to C γ -exo conformation, more favorable in the Yaa position, and 4S leads to a C γ -endo conformation more 91 (E) Oxime ligation cross-linking between 4S-aminooxyproline (Aop) and 4R-oxoacetamidoproline (Alp). 92 (F) Reversible Nterminal end-capping using a catechol for the cap and benzoboroxole on the peptide strand leading to boronate ester when reacted.…”

“…74−80 (C) Cysteine knot homotrimer cross-linking. 84−90 (D) Tricine on-resin C-terminal cross-linking 91. (E) Oxime ligation cross-linking between 4S-aminooxyproline (Aop) and 4R-oxoacetamidoproline (Alp) 92.…”

Coupling of a specific photoreactive triple-helical peptide to crosslinked collagen films restores binding and activation of DDR2 and VWF

“…End-stapling was carried out by coupling the tri-acid hexapeptide Fmoc-GFGEEG to three resin-supported strands. Addition of N-terminal templates in an attempt to covalently link the three peptide strands is known to be a difficult and slow reaction [ 49 ]. Previous attempts in our lab to end-staple peptides at their C-terminus by introducing two lysine residues gave poor results.…”