Chemistry of the collagen cross-links. Isolation and characterization of two intermediate intermolecular cross-links in collagen
TL;DR: The reduction of intact collagen fibrils with tritiated sodium borohydride was found to stabilize the aldehyde-mediated cross-links to acid hydrolysis and thus allowed their location and isolation from acid hydrolysates on an automatic amino acid analyser.
Abstract: This paper describes the isolation from reduced collagen of two new amino acids believed to be involved, in their non-reduced form, as intermolecular cross-links stabilizing the collagen fibre. The reduction of intact collagen fibrils with tritiated sodium borohydride was found to stabilize the aldehyde-mediated cross-links to acid hydrolysis and thus allowed their location and isolation from acid hydrolysates on an automatic amino acid analyser. Comparison of the radioactive elution patterns from the autoanalyser of collagen treated in various ways before reduction permitted a preliminary classification of the peaks into cross-link precursors, intramolecular and intermolecular cross-links. The techniques employed to isolate the purified components on a large scale and to identify them structurally are described in detail. Two labile intermolecular cross-links were isolated in their reduced forms, one of which was identified by high-resolution mass spectrometry as N(in)-(5-amino-5-carboxypentyl)hydroxylysine. The structure of this compound was confirmed by chemical synthesis. The cross-link precursor alpha-aminoadipic delta-semialdehyde was isolated in its reduced form, in-hydroxynorleucine, together with its acid degradation product in-chloronorleucine. A relatively stable intermolecular cross-link was isolated and partially characterized by mass spectrometry as an aldol resulting from the reaction of the delta-semialdehyde derived from lysine and hydroxylysine.
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TL;DR: Various levels of structural organization in collagen are described by means of a distinctive molecular conformation arising from special regularities in its amino acid sequence and their chemical basis.
Abstract: Publisher Summary Collagen is the major protein constituent of a wide range of vertebrate and invertebrate species and it occurs in diverse tissues such as bone, skin, tendon, cornea, and basement membrane. It has been implicated in morphogenesis and various complex regulatory mechanisms during growth and wound healing that the role of collagen in mature tissue is primarily structural. It fulfills this function by means of a distinctive molecular conformation arising from special regularities in its amino acid sequence. This chapter describes these various levels of structural organization in collagen and their chemical basis. The triple-stranded, coiled-coil structure of collagen as determined by X-ray diffraction is widely accepted. Its rodlike shape and dimensions of about 3000 X 15 A are also well established. However, the physical evidence says that in cross section the collagen molecule must contain three polypeptide chains. It does not indicate whether the chains are parallel or antiparallel, whether there are many short ones or perhaps one long chain folded back on it twice, or whether they are identical or nonidentical.
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TL;DR: Two sisters nine and 12 years of age presented with a similar clinical picture consisting of severe scoliosis, recurrent joint dislocation and hyperextensible skin and joints.
Abstract: Two sisters nine and 12 years of age presented with a similar clinical picture consisting of severe scoliosis, recurrent joint dislocation and hyperextensible skin and joints. Amino acid a...
377Â citations
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TL;DR: Current theories of the crosslinks stabilising the collagen fibre are based on the isolation of compounds from borohydride-reduced collagen but what is the evidence for their existence in vivo and what, if any, is the physiological significance of these proposed crosslinks both in normal and pathological conditions?
Abstract: Current theories of the crosslinks stabilising the collagen fibre are based on the isolation of compounds from borohydride-reduced collagen. What is the evidence for their existence in vivo and what, if any, is the physiological significance of these proposed crosslinks both in normal and pathological conditions?
319Â citations
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TL;DR: Micro-Heterogeneity in the Biosynthesis of Collagen Detailed analyses of the structure of the polypeptide chains of collagen has revealed a "micro-heterogeneity" of the amino acid sequences.
Abstract: Micro-Heterogeneity in the Biosynthesis of Collagen Detailed analyses of the structure of the polypeptide chains of collagen has revealed a "micro-heterogeneity" of the amino acid sequences. Sequen...
306Â citations
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TL;DR: The collagen produced in response to an injury of human skin is initially stabilized by a crosslink derived from hydroxyallysine, and characteristic of embryonic skin this article, which is typical of young skin collagen.
281Â citations