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Toward Activatable Collagen Mimics: Combining DEPSI “Switch” Defects and Template‐Guided Self‐Organization to Control Collagen Mimetic Peptides
Author(s) -
Röber Matthias,
Scheibel Thomas,
Börner Hans G.
Publication year - 2021
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.202100070
Subject(s) - chemistry , circular dichroism , structural motif , triple helix , peptide , biophysics , scaffold , folding (dsp implementation) , native chemical ligation , crystallography , stereochemistry , biochemistry , cysteine , medicine , enzyme , electrical engineering , biomedical engineering , biology , engineering
Collagen mimetic peptides (CMPs), which imitate various structural or functional features of natural collagen, constitute advanced models illuminating the folding aspects of the collagen triple helix (CTH) motif. In this study, the CMPs of repeating Gly–Pro–Pro (GPP) triplets are tethered to an organic scaffold based on a tris(2‐aminoethyl) amine (TREN) derivative (TREN(sucOH) 3 ). These three templated peptide strands are further expanded via native chemical ligation to increase the number of GPP triplets and lead to a TREN(sucGPPGPPG( Ψ )SPGPPCPP[GPP] 4 ) 3 construct. The incorporation of an ester switch segment, G( Ψ )S, as a positional O ‐acyl isopeptide (DEPSI) defect into the peptide strands allows the pH‐controlled acceleration of CTH formation. The strand assembly process is monitored by circular dichroism (CD) spectroscopy. The results of pH jump experiments and thermal denaturation studies provide new insights into the contributions of structural DEPSI defects to the template‐guided self‐assembly of the CTH motif. While the organic scaffold drives the CTH formation, the switch defects act as temporary opponents and slow down the folding. CD spectroscopy data confirm that the switch defects contribute to the formation of a more stable CTH motif by enhancing the structural dynamics at the early stage of the folding process.