Morphology of Osteogenesis Imperfecta Collagen Mimetic Peptide Assemblies Correlates with the Identity of Glycine‐Substituting Residue

Abstract

Osteogenesis imperfecta (OI) is a hereditary bone disorder with various phenotypes ranging from mild multiple fractures to perinatal lethal cases, and it mainly results from the substitution of Gly by a bulkier residue in type I collagen. Triple‐helical peptide models of Gly mutations have been widely utilized to decipher the etiology of OI, although these studies are mainly limited to characterizing the peptide features, such as stability and conformation in the solution state. Herein, we have constructed a new series of triple‐helical peptides DD(GPO)5ZPO(GPO)4DD (Z=Ala, Arg, Asp, Cys, Glu, Ser, and Val) mimicking the most common types of observed OI cases. The inclusion of special terminal aspartic acids enables these collagen mimetic peptides to self‐assemble to form nanomaterials upon the trigger of lanthanide ions. We have for the first time systematically evaluated the effect of different OI mutations on the aggregated state of collagen mimetic peptides. We have revealed that the identity of the Gly‐substituting residue plays a determinant role in the morphology and secondary structure of the collagen peptide assemblies, showing that bulkier residues tend to result in a disruptive secondary structure and defective morphology, which lead to more severe OI phenotypes. These findings of osteogenesis imperfecta collagen mimetic peptides in the aggregation state provide novel perspectives on the molecular mechanism of osteogenesis imperfecta, and may aid the development of new therapeutic strategies.

Effect of Nutraceutical Factors on Hepatic Intermediary Metabolism in Wistar Rats with Induced Tendinopathy

“…This fact explains why the DC group, which does not receive any treatment, has higher levels of G6PDH activity in the late phase (Phase III) of the disease. However, the group treated with AA, which are involved in the formation of collagen synthesis, was able to regenerate the tendon more rapidly, and therefore reduce the presence of enzymes associated with damage [ 33 ]. Some authors have observed that type I collagen in TP mice increases after administration of Gly, improving the biomechanical properties of the tendon and the degree of fiber compaction [ 18 ].…”

“…This effect can be explained by the relationship of amino acids in obtaining energy from the beta-oxidation of fatty acids. The group treated with AA could be provided with these compounds for early energy production and greater tendon recovery thanks to the decomposition of glycine and aspartic acid to enter these metabolic pathways and thus adapt to energy needs [ 33 ].…”

Heterotrimeric collagen peptides: design, characterization, and applications

“…三螺旋结构胶原多肽在静电 相互作用下自组装形成纳米纤维, 从而模拟了胶原蛋 白的纤维结构 [26,27] . 在自组装胶原多肽序列中引入Gly 突变后会影响其三螺旋结构稳定性和纤维形貌的形 成, 并使其失去生物活性, 可以用于研究OI突变的机 制 [28] . 然而大部分仿生胶原蛋白的胶原多肽都是同源…”