{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:47:47Z","timestamp":1790722067303,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[1998,9,1]],"date-time":"1998-09-01T00:00:00Z","timestamp":904608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[1998,9,1]],"date-time":"1998-09-01T00:00:00Z","timestamp":904608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharm Res"],"published-print":{"date-parts":[[1998,9]]},"DOI":"10.1023\/a:1011918108849","type":"journal-article","created":{"date-parts":[[2002,12,23]],"date-time":"2002-12-23T06:29:09Z","timestamp":1040624949000},"page":"1456-1462","source":"Crossref","is-referenced-by-count":16,"title":["Chemical Degradation Kinetics of Recombinant Hirudin (HVI) in Aqueous Solution: Effect of pH"],"prefix":"10.1007","volume":"15","author":[{"given":"Ursula","family":"Gietz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Alder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Langguth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor","family":"Arvinte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans P.","family":"Merkle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"304001_CR1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/BF00630151","volume":"42","author":"F. Markwardt","year":"1955","unstructured":"F. Markwardt. Untersuchungen \u00fcber Hirudin. Naturwissenschaften\n42:537\u2013538 (1955).","journal-title":"Naturwissenschaften"},{"key":"304001_CR2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1055\/s-2007-1002594","volume":"17","author":"W. E. M\u00e4rki","year":"1991","unstructured":"W. E. M\u00e4rki, H. Grossenbacher, M. G. Gr\u00fctter, M. H. Liersch, B. Meyhack, and J. Heim. Recombinant hirudin: genetic engineering and structure analysis. Semin. Thromb. Hemostasis\n17:88\u201393 (1991).","journal-title":"Semin. Thromb. Hemostasis"},{"issue":"17","key":"304001_CR3","doi-asserted-by":"crossref","first-page":"10839","DOI":"10.1016\/S0021-9258(18)99095-2","volume":"266","author":"J.-Y. Chang","year":"1991","unstructured":"J.-Y. Chang. Stability of hirudin, a thrombin-specific inhibitor. J. Biol. Chem.\n266(17):10839\u201343 (1991).","journal-title":"J. Biol. Chem."},{"key":"304001_CR4","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/rcm.1290071205","volume":"7","author":"H. Grossenbacher","year":"1993","unstructured":"H. Grossenbacher, W. M\u00e4rki, M. Coulot, D. M\u00fcller, and W. J. Richter. Characterization of succinimide-type dehydration products of recombinant hirudin variant 1 by electrospray tandem mass spectrometry. Rapid Communications in Mass Spectrometry\n7:1082\u20131085 (1993).","journal-title":"Rapid Communications in Mass Spectrometry"},{"key":"304001_CR5","doi-asserted-by":"crossref","unstructured":"S. Capasso, L. Mazzarella, F. Sica, A. Zagari, and S. Salvadori. Spontaneous cyclization of the aspartic acid side chain to the succinimide derivative. J. Chem. Soc. Chem. Commun. 919\u2013921 (1992).","DOI":"10.1039\/c39920000919"},{"issue":"2","key":"304001_CR6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0021-9258(19)75855-4","volume":"262","author":"T. Geiger","year":"1987","unstructured":"T. Geiger and St. Clarke. Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. J. Biol. Chem.\n262(2):785\u2013794 (1987).","journal-title":"J. Biol. Chem."},{"key":"304001_CR7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/prot.340050103","volume":"5","author":"S. J. Wearne","year":"1989","unstructured":"St. J. Wearne and T. E. Creighton. Effect of protein conformation on rate of deamidation: Ribonuclease A. Proteins\n5:8\u201312 (1989).","journal-title":"Proteins"},{"key":"304001_CR8","doi-asserted-by":"crossref","first-page":"8955","DOI":"10.1021\/ja9606182","volume":"118","author":"M. Xie","year":"1996","unstructured":"M. Xie, D. V. Velde, M. Morton, R. T. Borchardt, and R. L. Schowen. pH-induced change in the rate-determining step for the hydrolysis of the Asp\/Asn-derived cyclic-imide intermediate in protein degradation. J. Am. Chem. Soc.\n118:8955\u20138956 (1996).","journal-title":"J. Am. Chem. Soc."},{"key":"304001_CR9","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/(SICI)1096-9888(199609)31:9<967::AID-JMS381>3.0.CO;2-K","volume":"24","author":"P. Schindler","year":"1996","unstructured":"P. Schindler, D. M\u00fcller, W. M\u00e4rki, H. Grossenbacher, and W. J. Richter. Characterization of a \u03b2-Asp33 isoform of recombinant hirudin sequence Variant 1 by low-energy collision-induced dissociation. J. Mass Spectrom.\n24:967\u2013974 (1996).","journal-title":"J. Mass Spectrom."},{"key":"304001_CR10","doi-asserted-by":"crossref","first-page":"8291","DOI":"10.1021\/bi00150a024","volume":"31","author":"A. Tuong","year":"1992","unstructured":"A. Tuong, M. Maftouh, C. Ponthus, O. Whitechurch, C. Roitsch, and C. Picard. Characterization of the deamidated forms of recombinant hirudin. Biochemistry\n31:8291\u20138299 (1992).","journal-title":"Biochemistry"},{"key":"304001_CR11","first-page":"41","volume-title":"Spectroscopic and related studies of recombinant hirudin, human neuropeptide Y and analogues","author":"A. P. Nordmann","year":"1996","unstructured":"A. P. Nordmann. Spectroscopic and related studies of recombinant hirudin, human neuropeptide Y and analogues, Ph.D. Thesis, Birkbeck College, London, 1996, p. 41."},{"key":"304001_CR12","first-page":"31","volume-title":"The effect of solution environment on the stability and aggregation of recombinant human interleukin-2","author":"S. J. Advant","year":"1994","unstructured":"S. J. Advant. The effect of solution environment on the stability and aggregation of recombinant human interleukin-2. Ph.D. Thesis, University of Connecticut, U.M.I. Publ., Ann Arbor (MI), USA, 1994, pp. 31\u201334."},{"issue":"1","key":"304001_CR13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0049-3848(94)90032-9","volume":"74","author":"F. Markwardt","year":"1994","unstructured":"F. Markwardt. The development of hirudin as an antithrombotic drug. Thromb. Res.\n74(1):1\u201323 (1994).","journal-title":"Thromb. Res."},{"key":"304001_CR14","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1021\/bi00436a027","volume":"28","author":"H. Haruyama","year":"1989","unstructured":"H. Haruyama and K. W\u00fcthrich. Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance. Biochemistry\n28:4301\u20134312 (1989).","journal-title":"Biochemistry"},{"key":"304001_CR15","unstructured":"K. Forrer, P. Girardot, M. Dettwiler, W. M\u00e4rki, H. Grossenbacher, and E. Gassmann. Different modes of capillary electrophoresis for the analysis of recombinant hirudin. 9th International Symposium on Capillary Electrophoresis. Budapest, Hungary. 1994."},{"key":"304001_CR16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0021-9673(94)01261-C","volume":"700","author":"C. Dette","year":"1995","unstructured":"C. Dette and H. W\u00e4tzig. Separation of r-hirudin from similar substances by capillary electrophoresis. J. Chromatogr. A\n700:89\u201394 (1995).","journal-title":"J. Chromatogr. A"},{"key":"304001_CR17","volume-title":"Therapeutic protein formulation for sustained delivery: Formulation aspects and stability","author":"U. Gietz","year":"1997","unstructured":"U. Gietz. Therapeutic protein formulation for sustained delivery: Formulation aspects and stability. Ph.D. Thesis, Department of Pharmacy ETH, Z\u00fcrich, 1997."},{"key":"304001_CR18","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/j.1399-3011.1987.tb03390.x","volume":"30","author":"S. Clarke","year":"1987","unstructured":"S. Clarke. Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins. Int. J. Peptide Protein Res.\n30:808\u2013821 (1987).","journal-title":"Int. J. Peptide Protein Res."},{"key":"304001_CR19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1126\/science.3353715","volume":"240","author":"A. A. Kossiakoff","year":"1988","unstructured":"A. A. Kossiakoff. Tertiary structure is a principal determinant to protein deamidation. Science\n240:191\u2013194 (1988).","journal-title":"Science"},{"key":"304001_CR20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1023\/A:1018981231468","volume":"10","author":"C. Oliyai","year":"1993","unstructured":"C. Oliyai and R. T. Borchardt. Chemical pathways of peptide degradation. IV. Pathways, kinetics and mechanism of degradation of an aspartyl residue in a model hexapeptide. Pharm. Res.\n10:95\u2013102 (1993).","journal-title":"Pharm. Res."},{"key":"304001_CR21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/pro.5560020305","volume":"2","author":"T. V. Brennan","year":"1993","unstructured":"T. V. Brennan and St. Clarke. Spontaneous degradation of poly-peptides at aspartyl and asparaginyl residues: Effect of the solvent dielectric. Protein Sci.\n2:331\u2013338 (1993).","journal-title":"Protein Sci."},{"key":"304001_CR22","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1126\/science.4001942","volume":"228","author":"T. J. Ahern","year":"1985","unstructured":"T. J. Ahern and A. M. Klibanov. The mechanism of irreversible enzyme inactivation at 100\u00b0C. Science\n228:1280\u20131284 (1985).","journal-title":"Science"},{"key":"304001_CR23","first-page":"1","volume-title":"Stability and characterization of protein and peptide drugs","author":"R. Pearlman","year":"1993","unstructured":"R. Pearlman and T. A. Bewley. Stability and characterization of human growth hormone. In: Y. J. Wang and R. Pearlman (eds.), Stability and characterization of protein and peptide drugs, Plenum Press, New York, 1993, pp 1."},{"issue":"12","key":"304001_CR24","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1023\/A:1018903014204","volume":"11","author":"R. I. Senderoff","year":"1994","unstructured":"R. I. Senderoff, S. C. Wootton, A. M. Boctor, T. M. Chen, A. B. Giordani, T. N. Julian, and G. W. Radebaugh. Aqueous stability of human epidermal growth factor 1\u201348. Pharm. Res.\n11(12):1712\u20131720 (1994).","journal-title":"Pharm. Res."},{"key":"304001_CR25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1432-1033.1991.tb16345.x","volume":"202","author":"A. Otto","year":"1991","unstructured":"A. Otto and R. Seckler. Characterization, stability and refolding of recombinant hirudin. Eur. J. Biochem.\n202:67\u201373 (1991).","journal-title":"Eur. J. Biochem."},{"key":"304001_CR26","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/pro.5560040612","volume":"4","author":"R. Khurana","year":"1995","unstructured":"R. Khurana, A. T. Hate, U. Nath, and J. B. Udgaonkar. pH dependence of the stability of barstar to chemical and thermal denaturation. Protein Science\n4:1133\u20131144 (1995).","journal-title":"Protein Science"}],"container-title":["Pharmaceutical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1023\/A:1011918108849.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1023\/A:1011918108849\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1023\/A:1011918108849.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T07:36:02Z","timestamp":1754033762000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1023\/A:1011918108849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1998,9]]}},"alternative-id":["304001"],"URL":"https:\/\/doi.org\/10.1023\/a:1011918108849","relation":{},"ISSN":["0724-8741","1573-904X"],"issn-type":[{"value":"0724-8741","type":"print"},{"value":"1573-904X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,9]]}}}