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The Biochemical Journal Aug 1978Desmosine-enriched peptides were isolated from a thermolysin digest of bovine ligamentum nuchae elastin and a partial sequence was determined. A 'two-cross-link' model...
Desmosine-enriched peptides were isolated from a thermolysin digest of bovine ligamentum nuchae elastin and a partial sequence was determined. A 'two-cross-link' model is proposed in which a second cross-link, perhaps lysinonorleucine, joins two peptide chains approx. 35 amino acid residues removed from the desmosine. Implied in this model is a certain asymmetry or directionality which places restrictions on the 'sense' of the peptide chains (either always parallel or anti-parallel) in order to align the cross-linking sites. Imposing such restrictions raises the possibility of specific alignment of elastin precursor molecules by microfibrillar proteins and/or aligning peptides on the precursor molecules themselves.
Topics: Amino Acid Sequence; Chromatography, Ion Exchange; Desmosine; Elastin; Models, Molecular; Peptide Fragments; Thermolysin
PubMed: 697739
DOI: 10.1042/bj1730617 -
Chemical Communications (Cambridge,... Mar 2012Desmosine, a crosslinking amino acid of elastin, is an attractive biomarker for diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the first total...
Desmosine, a crosslinking amino acid of elastin, is an attractive biomarker for diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the first total synthesis of (+)-desmosine was achieved in 11% overall yield in 13 steps utilizing stepwise and regioselective Sonogashira cross-coupling reactions.
Topics: Biomarkers; Cross-Linking Reagents; Desmosine; Elastin; Molecular Structure; Pulmonary Disease, Chronic Obstructive; Stereoisomerism
PubMed: 22353933
DOI: 10.1039/c2cc17958j -
Respiratory Medicine Feb 2002Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin...
Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects ofthe exacerbation on ventilatory function. The mean (SD) FEV1 was 45 (15)% predicted during the exacerbation and 57.8 (16)% predicted 2 months later (P=0.00001). The mean (SD) DES excretion was 25.3 (9) microg g(-1) creatinine at day 1;23.5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20.9 (7) microg g(-1) creatinine (P=0.049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3.2 microg g(-1) creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.
Topics: Acute Disease; Aged; Analysis of Variance; Biomarkers; Chromatography, Micellar Electrokinetic Capillary; Desmosine; Elastin; Forced Expiratory Volume; Humans; Longitudinal Studies; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive
PubMed: 11860167
DOI: 10.1053/rmed.2001.1224 -
The Journal of Biological Chemistry Oct 1966
Topics: Amino Acids; Animals; Aorta; Chick Embryo; Culture Techniques; Elastin; Lysine
PubMed: 5926173
DOI: No ID Found -
Journal of Chromatography. B,... Jun 1995A method has been developed for the enrichment and analysis of the elastin crosslinks, desmosine and isodesmosine, in biological fluids and tissues. It is adapted from...
A method has been developed for the enrichment and analysis of the elastin crosslinks, desmosine and isodesmosine, in biological fluids and tissues. It is adapted from published methods, offering improved recovery, sensitivity, resolution, and speed of analysis. Samples were hydrolyzed in 6 M HCl, after which the desmosines were enriched by CF1 cellulose chromatography and analyzed by HPLC with a C18 column. Isodesmosine and desmosine were quantitated based on absorbance at 275 nm, with a limit of detection of approximately 30 pmol and recovery of approximately 66% in urine. Their tR values on our HPLC system were approximately 9 and 12 min, respectively. This method was used to evaluate the daily and weekly variation in the concentrations of desmosine and isodesmosine in human urine. The results suggest that this method can be used to process large numbers of biological samples for analysis of desmosine and isodesmosine.
Topics: Animals; Body Fluids; Chromatography, High Pressure Liquid; Cricetinae; Desmosine; Humans; Isodesmosine; Lung; Reference Values; Reproducibility of Results; Spectrophotometry, Ultraviolet
PubMed: 7581855
DOI: 10.1016/0378-4347(95)00092-w -
Chest May 2007Application of mass spectrometry (MS) for direct measurements of desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of elastin degradation in...
OBJECTIVES
Application of mass spectrometry (MS) for direct measurements of desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of elastin degradation in patients with alpha(1)-antitrypsin deficiency (AATD) and non-AATD-related COPD.
BACKGROUND
In COPD patients, the lungs undergo elastin injury, which can be monitored by measurements of D and I in body fluids as specific markers of elastin degradation using the specificity and sensitivity of MS.
METHODS
Acid hydrolysis of blood plasma, 24-h urine and sputum measurements, followed by chromatographic separation for mass spectrometric analysis.
RESULTS
Each patient group had levels of plasma D and I that were statistically significantly higher than those of control subjects. AATD patients had higher levels than COPD patients with normal alpha(1)-antitrypsin (AAT) levels. Twenty-four-hour urine measurements demonstrated no significant difference in total levels of D and I among control subjects and patients but showed a free (unbound) concentration of D and I in urine, which was statistically significantly higher in patients with COPD with and without AAT. The D and I levels in the sputum of patients with AATD exceeded the levels in COPD patients with normal AAT levels.
CONCLUSIONS
MS allows a sensitive and specific analysis of D and I in body fluids. The quantification of D and I in sputum, along with increases of D and I in plasma and an elevated free component of D and I in urine provide indexes that characterize patients with COPD and can be followed in relation to the course of the disease and/or therapy.
Topics: Adult; Aged; Aged, 80 and over; Desmosine; Elastin; Female; Humans; Isodesmosine; Male; Mass Spectrometry; Matched-Pair Analysis; Middle Aged; Prognosis; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity; Sputum; alpha 1-Antitrypsin Deficiency
PubMed: 17494786
DOI: 10.1378/chest.06-2251 -
Methods in Enzymology 1982
Topics: Amino Acids; Animals; Antibody Formation; Desmosine; Elastin; Radioimmunoassay
PubMed: 7078455
DOI: 10.1016/0076-6879(82)82100-9 -
Respiratory Medicine Jun 2021A previous 2-week clinical trial of aerosolized hyaluronan (HA) in COPD showed a rapid reduction in lung elastic fiber breakdown, as measured by sputum levels of the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
A previous 2-week clinical trial of aerosolized hyaluronan (HA) in COPD showed a rapid reduction in lung elastic fiber breakdown, as measured by sputum levels of the unique elastin crosslinks, desmosine and isodesmosine (DID). To further assess the therapeutic efficacy of HA and the utility of DID as surrogate markers for the development of pulmonary emphysema, we have conducted a 28-day randomized, double-blind, placebo-controlled, phase 2 trial of HA involving 27 subjects with alpha-1 antiprotease deficiency COPD.
METHODS
The study drug consisted of a 3 ml inhalation solution containing 0.03% HA with an average molecular weight of 150 kDa that was self-administered twice daily. DID levels were measured in urine, sputum, and plasma using tandem mass spectrometry.
RESULTS
Free urine DID in the HA group showed a significant negative correlation with time between days 14 and 35 (r = -1.0, p = 0.023) and was statistically significantly decreased from baseline at day 35 (15.4 vs 14.2 ng/mg creatinine, p = 0.035). A marked decrease in sputum DID was also seen in the HA group between days 1 and 28 (0.96 vs 0.18 ng/mg protein), but the difference was not significant, possibly due to the small number of adequate specimens. Plasma DID remained unchanged following HA treatment and no significant reductions in urine, sputum, or plasma DID were seen in the placebo group.
CONCLUSIONS
The results support additional clinical trials to further evaluate the therapeutic effect of HA and the use of DID as a real-time marker of drug efficacy.
Topics: Administration, Inhalation; Adult; Aerosols; Aged; Biomarkers; Desmosine; Double-Blind Method; Female; Humans; Hyaluronic Acid; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Time Factors; Treatment Outcome; alpha 1-Antitrypsin Deficiency
PubMed: 33906126
DOI: 10.1016/j.rmed.2021.106402 -
HSS Journal : the Musculoskeletal... Sep 2010The objective of this prospective observational study was to determine if urine desmosine levels, a marker of lung injury, increase in response to the periopreative...
The objective of this prospective observational study was to determine if urine desmosine levels, a marker of lung injury, increase in response to the periopreative insults of anterior and posterior spine surgery. Desmosine, a stable breakdown product of elastin, has been proposed as a surrogate marker of lung injury in patients with COPD, tobacco use, and ARDS. We recently evaluated this marker in patients undergoing knee surgery, but the utility of desmosine as a marker of lung injury in patients undergoing spine surgery remains unstudied. In this study, we enrolled ten consecutive patients, who underwent anterior/posterior spine surgery. Patient demographics and perioperative data were recorded. Urine samples were collected at baseline, 1 day, and 3 days postoperatively and analyzed for levels of desmosine using a previously validated radioimmunoassay. Desmosine levels were 35.9 ± 18.2 pmol/mg creatinine at baseline, 38.7 ± 11 pmol/mg creatinine on postoperative day 1, and 70.5 ± 49.1 pmol/mg creatinine on postoperative day 3, respectively. Desmosine/creatinine ratios measured on day 3 postoperatively were significantly elevated compared to levels at baseline, and represented a 96.3% increase. No difference was seen between levels at baseline and day 1 postoperatively. In conclusion, we were able to show a significant increase in urine desmosine levels associated with anterior/posterior spine surgery. In the context of previous studies, our findings suggest that desmosine may be a marker of lung injury in this setting. However, further research is warranted for validation and correlation of desmosine levels to clinical markers and various degrees of lung injury.
PubMed: 21886530
DOI: 10.1007/s11420-010-9158-z -
The European Respiratory Journal Jun 2000Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are...
Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p< or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.
Topics: Adult; Aged; Aged, 80 and over; Bronchiectasis; Cross-Linking Reagents; Cross-Sectional Studies; Cystic Fibrosis; Desmosine; Elastin; Electrophoresis, Capillary; Emphysema; Extracellular Matrix; Female; Humans; Isodesmosine; Longitudinal Studies; Lung Diseases, Obstructive; Male; Middle Aged; alpha 1-Antitrypsin Deficiency
PubMed: 10885422
DOI: 10.1034/j.1399-3003.2000.01511.x