Abstract: The present invention relates to a method for preparing a modified folded protein, comprising modifying unfolded a-chains comprising a collagenous amino acid sequence and thereafter folding at least part of the modified a-chains into a quaternary protein structure, in particular a helical protein structure. The invention allows for an attractive alternative for making recombinant proteins, such as recombinant collagens and the like, which may be used in a variety of biomedical and other applications.

Abstract: The present invention relates to the gene PLOD2 which codes for telopeptide lysyl hydroxylase (TLH). This enzyme converts telopeptidyl Lys into telopeptidyl Hyl, that can subsequently be converted into hydroxyallysine cross-links. Collagen with hydroxyallysine cross-links shows a higher resistance to degradation by proteinases than collagen with cross-links derived from allysine. In one aspect, the invention provides methods and compositions to prepare collagenous materials with varying biodegradation rates by varying the ratio of hydroxyallysine cross-links over allysine cross-links. In another aspect, the invention provides methods and compositions to lower the ratio of hydroxyallysine cross-links over allysine cross-links in fibrotic processes, in order to obtain a collagenous network that is more easy to degrade.

Abstract: The present invention relates to a method for preparing a modified folded protein, comprising modifying unfolded a-chains comprising a collagenous amino acid sequence and thereafter folding at least part of the modified a-chains into a quaternary protein structure, in particular a helical protein structure. The invention allows for an attractive alternative for making recombinant proteins, such as recombinant collagens and the like, which may be used in a variety of biomedical and other applications.

Abstract: The present invention relates to the gene PLOD2 which codes for telopeptide lysyl hydroxylase (TLH). This enzyme converts telopeptidyl Lys into telopeptidyl Hyl, that can subsequently be converted into hydroxyallysine cross-links. Collagen with hydroxyallysine cross-links shows a higher resistance to degradation by proteinases than collagen with cross-links derived from allysine. In one aspect, the invention provides methods and compositions to prepare collagenous materials with varying biodegradation rates by varying the ratio of hydroxyallysine cross-links over allysine cross-links. In another aspect, the invention provides methods and compositions to lower the ratio of hydroxyallysine cross-links over allysine cross-links in fibrotic processes, in order to obtain a collagenous network that is more easy to degrade.

Abstract: The invention uses the existence of tissue-specific telopeptide lysyl hydroxylases, enzymes that hydroxylate lysine residues of the telopeptides of collagen, and the discovery that collagen molecules cross-linked by hydroxyallysine (derived from telopeptide hydroxylysine) are less susceptible to degradation/turnover than collagen molecules cross-linked by means of allysine (derived from telopeptide lysine) due to a different intrafibrillar packing of said collagen molecules. Further, the invention contemplates that one of the characteristics of collagen in scars and other fibrotic tissues is an increase in hydroxyallysine derived cross-links (making the collagen less susceptible to proteolytic breakdown), that this increase in hydroxyallysine cross-links is due to increased levels of telopeptide lysyl hydroxylase, and that telopeptide lysyl hydroxylase plays an important role in the excessive accumulation of collagen in fibrosis/scarring.

Abstract: The present invention relates to the gene PLOD2 which codes for telopeptide lysyl hydroxylase (TLH). This enzyme converts telopeptidyl Lys into telopeptidyl Hyl, that can subsequently be converted into hydroxyallysine cross-links. Collagen with hydroxyallysine cross-links shows a higher resistance to degradation by proteinases than collagen with cross-links derived from allysine.